Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies.

A prospective observational study (ClinicalTrial ID: NCT05771415) was conducted to compare placental oxygenation in low-risk, uncomplicated term pregnancies measured by near-infrared spectroscopy (NIRS) in relation to the placental maturity grade determined by ultrasound assessment according to the Grannum scale. We included 34 pregnancies divided into two groups according to placental maturation. For each pregnancy, measurements were taken at the site above the central part of the placenta (test) and at the site outside of the placenta on the lower abdomen (control). Student's t-test was used to compare tissue oxygenation index (TOI) values among the study groups. The normality of distribution was proven by the Kolmogorov‒Smirnov test. In women with low placental maturity grade, the mean TOI value above the placenta was 70.38 ± 3.72, which was lower than the respective value in women with high placental maturity grade (77.99 ± 3.71; p < 0.001). The TOI values above the placenta and the control site were significantly different in both groups (70.38 ± 3.72 vs 67.83 ± 3.21 and 77.99 ± 3.71 vs 69.41 ± 3.93; p < 0.001). The results offer a new perspective on placental function based on specific non-invasive real-time oxygenation measurements. Unfortunately, and because of technical limitations, NIRS cannot yet be implemented as a routine clinical tool.

Does COVID-19 infection acquired in different pregnancy trimester influence placental pathology?

OBJECTIVES: To determine the morphological characteristics of the placentas from COVID-19 positive mothers in regard to the trimester of COVID-19 infection onset and low weight molecular heparin (LMWH) treatment. METHODS: Placentas were collected in the period April 1st till September 1st 2021 after delivery at Department of Obstetrics and Gynecology University Hospital Split, Croatia, and sent for pathological examination. Medical history and pathology reports were used to collect the data. Pregnant women were divided based on the onset of COVID-19 infection and stratified into low molecular weight heparin (LMWH)+ or LMWH-. Depending on the data distribution, the following test were used: chi-squared test. Student's t-test, Mann-Whitney U test, ANOVA and Kruskal-Wallis test. RESULTS: In 38% of patients the onset of COVID-19 infection was the 1st trimester of pregnancy, in 27% in the 2nd and 35% of women were infected in the 3rd trimester The fetal vascular malperfusion (FVM) occurrence was statistically significantly higher in the LMWH- group and if the onset of infection was in the 2nd trimester, while the perivillous fibrin deposition was most likely to happen if the COVID-19 infection that occured in the 1st trimester of pregnancy. CONCLUSIONS: The onset of COVID-19 infection has the influence on trophoblast damage and subsequent morphological appearance of the placenta. LMWH use in COVID positive pregnant women decreases the rate of the FVM in examined placentas.

Vitamin B12 Supplementation in Addition to Folic Acid and Iron Improves Hematological and Biochemical Markers in Pregnancy: A Randomized Controlled Trial.

Vitamin B12 plays an important role in cell division and is of vital importance during pregnancy. Iron and B12 deficiency increase the risk of neonatal morbidity and the outcome of the overall pregnancy. The aim of our study was to analyze whether the use of vitamin B12, with standard supplements of folic acid and iron among nonanemic pregnant women, will result in improvements of hemogram parameters in terms of hematological and biochemical markers. Study participants were 200 healthy pregnant women, randomized into an intervention group and a control group, recruited from gynecological primary care practices in Split, Croatia. In addition to standard supplementation (350 mg/day ferrous iron, 5 mg folic acid), participants in the intervention group were given 5 µg of vitamin B12 each morning for 100 days. Both biochemical and hematological measurings were conducted in two intervals: 8th-10th week of gestation and then again in the 34th-36th week of gestation. Participants in the control group were given only standard-of-care iron and folic acid supplementation. Significantly lower values of haptoglobin postintervention, compared with baseline, were found only in the intervention group; for erythrocytes, significantly lower values postintervention were found only in the control group. For parameter hematocrit, we found decreased values postintervention, compared with baseline, in both intervention and control group; however, this decrease was within the reference range for the control group, whereas it was above the reference range for the intervention group. The results of this study indicated that intervention with vitamin B12 in pregnancy reduces possibilities of the onset of anemia, but within reference range.

Spontaneous Heterotopic Pregnancy as an Uncommon Clinical Problem.

BACKGROUND: Heterotopic pregnancy refers to the simultaneous coexistence of an intrauterine and extrauterine pregnancy. In natural conception it is very rare, with a rising incidence in patients undergoing assisted reproduction technologies. It presents a serious diagnostic problem which is often misdiagnosed. Currently, there are no standard protocols for the treatment and diagnosis of heterotopic pregnancy. METHODS: Two rare cases of spontaneous heterotopic pregnancy are presented. RESULT: The first patient had a complete abortion upon which an extrauterine pregnancy was detected. The second patient, after an extrauterine pregnancy removal, progressed with an intrauterine pregnancy until full term and it ended with the delivery of a healthy infant. CONCLUSION: Two demonstrated cases underscore that whenever abnormal adnexal findings are presented and the beta-hCG blood test is positive, the possibility of a heterotopic pregnancy should be suspected.

Maternal body mass index change as a new optimal gestational weight gain predictor in overweight women.

AIM: To investigate the relationship between maternal pre-pregnancy body-mass index (BMI) and neonatal birth weight. METHODS: The observational study included 2906 mothers and their neonates born from 2005 to 2011 at the Department of Gynecology and Obstetrics, Split University Hospital Center. Mothers with singleton term pregnancies who were overweight before pregnancy (BMI 25-29.9 kg/m2) were compared with those with normal pre-pregnancy weight (BMI 18.5-24.9 kg/m2). BMI change was assessed as a predictor of birth weight, categorized as small (SGA), appropriate (AGA), or large for gestational age (LGA). RESULTS: The rate of SGA infants was significantly lower (n=199; 6.8% vs n=1548; 9.2%) and the rate of LGA infants significantly greater among pre-pregnancy overweight mothers compared with normal-weight mothers (n=371; 12.8% vs n=1302; 7.8%; P<0.001 both). Overweight mothers had a significant probability of delivering an SGA neonate when they gained less than 6 kg, as compared with 8 kg among normal-weight mothers. They had a significant probability of delivering an LGA neonate when they gained more than 14 kg, compared with more than 20 kg among normal-weight mothers. BMI change was a more consistent indicator, suggesting that the ranges of 3.0-7.9 kg/m2 in overweight and 2-5.9 kg/m2 in normal-weight women were not associated with a significant increase in the rate of SGA or LGA. CONCLUSION: Maternal height seems to be an important factor in optimal weight gain definition, suggesting that BMI change should be a preferred measure of pregnancy-related weight.

A Retrospective Study of Discordant Twin Growth in Dichorionic Twin Pregnancies and Risk of Preterm Delivery at Split University Hospital Centre: Three-Year Experience.

The aim was to determine whether discordant twin growth has an impact on preterm birth in dichorionic pregnancies. This retrospective study included dichorionic twin pregnancies in the period from January 1, 2013 to December 31, 2015. The following variables were investigated: maternal age (years), parity, body mass index (kg/m2), week (≤366/7 and ≥37) and mode of delivery (vaginal and cesarean section), birth weight (grams) and Apgar score (≤7, 8-10). Discordant twin growth in dichorionic pregnancies was found to be associated with preterm birth (χ2=4.74; p=0.03) but had no impact on the mode of delivery (χ2=0.119; p=0.73). There was a statistically significant difference in the rate of small for gestational age (SGA) neonates (χ2=16.4556; p=0.000267) and Apgar score (χ2=7.9931; p<0.05) between the study groups. Mode of conception in dichorionic pregnancies was not a risk factor for preterm delivery (χ2=1.417; p=0.23). In conclusion, discordant twin growth in dichorionic pregnancies is a risk factor for preterm delivery and has no impact on the mode of delivery but has an impact on the rate of SGA and Apgar score.

Calculation of optimal gestation weight gain in pre-pregnancy underweight women due to body mass index change in relation to mother's height.

BACKGROUND: Optimal gestational weight gain has not yet been clearly defined and remains one of the most controversial issues in modern perinatology. The role of optimal weight gain during pregnancy is critical, as it has a strong effect on perinatal outcomes. PURPOSE: In this study, gestational body mass index (BMI) change, accounting for maternal height, was investigated as a new criterion for gestational weight gain determination, in the context of fetal growth assessment. We had focused on underweight women only, and aimed to assess whether the Institute of Medicine (IOM) guidelines could be considered acceptable or additional corrections are required in this subgroup of women. METHODS: The study included 1205 pre-pregnancy underweight mothers and their neonates. Only mothers with singleton term pregnancies (37th-42nd week of gestation) with pre-gestational BMI < 18.5 kg/m2 were enrolled. RESULTS: The share of small for gestational age (SGA) infants in the study population was 16.2 %. Our results showed the minimal recommended gestational weight gain of 12-14 kg and BMI change of 4-5 kg/m2 to be associated with a lower prevalence of SGA newborns. Based on our results, the recommended upper limit of gestational mass change could definitely be substantially higher. CONCLUSION: Optimal weight gain in underweight women could be estimated in the very beginning of pregnancy as recommended BMI change, but recalculated in kilograms according to body height, which modulates the numerical calculation of BMI. Our proposal presents a further step forward towards individualized approach for each pregnant woman.

The Impact of Inherited Thrombophilia Types and Low Molecular Weight Heparin Treatment on Pregnancy Complications in Women with Previous Adverse Outcome.

PURPOSE: To assess the distribution of births and spontaneous abortions, first-trimester abortion (FTA) and mid-trimester abortion (MTA), in untreated (n=128) and low molecular weight heparin (LMWH) treated pregnancies (n=50) of the same women with inherited thrombophilias and adverse pregnancy outcome (APO) in previous pregnancies. We particularly investigated the impact of LMWH on reducing the pregnancy complications in two thrombophilia types, "Conventional" and "Novel". MATERIALS AND METHODS: 50 women with inherited thrombophilia (26 Conventional and 24 Novel) and APO in previous pregnancies were included in the study. Conventional group included factor V Leiden (FVL), prothrombin G20210A (PT) mutations and antithrombin (AT), protein S (PS), and protein C (PC) deficiency, while the Novel group included methylentetrahydrofolate-reductase (MTHFR), plasminogen activator inhibitor-1 (PAI-1), and angiotensin converting enzyme (ACE) polymorphism. APO was defined as one of the following: preterm birth (PTB), fetal growth restriction (FGR), preeclampsia (PE), intrauterine fetal death (IUFD), placental abruption (PA) and deep venous thrombosis (DVT). RESULTS: There was no difference in distribution of births and spontaneous abortions between Conventional and Novel thrombophilia in untreated pregnancies (χ²=2.7; p=0.100) and LMWH treated pregnancies (χ²=0.442; p=0.506). In untreaed pregnancies thrombophilia type did not have any impact on the frequency of FTA and MTA (χ²=0.14; p=0.711). In birth-ended pregnancies LMWH treatement reduced the incidence of IUFD (p=0.011) in Conventional and FGR, IUFD, and PTB in Novel thrombophilia group. CONCLUSION: The equal impact of two thrombophilia types on the pregnancy outcomes and a more favorable effect of LMWH therapy on pregnancy complications in Novel thrombophilia group point the need for Novel thrombophilias screening and the future studies on this issue should be recommended.

Fas and FasL expression in placentas complicated with intrauterine growth retardation with and without preeclampsia.

OBJECTIVE: To compare the level of Fas and FasL immunohistochemical expression in villous trophoblast (VT), extravillous trophoblast (EVT) cells, decidual cells (DC), endothelial cells (EC) of villous blood vessels and spiral arteries between the study groups of intrauterine growth retardation (IUGR) placentas with and without preeclampsia (PE). METHODS: The study included 17 placentas from pregnancies complicated by IUGR + PE and 17 placentas from pregnancies complicated by idiopathic IUGR (I-IUGR). Seventeen placentas from normal pregnancies served as a control group. CD31 was used to detect endothelial cells (EC). Immunohistochemical expression of Fas and FasL was assessed in all examined parts of placenta using the semi-quantitative HSCORE method. RESULTS: FasL expression was significantly higher in all examined parts of placenta in I-IUGR as compared to IUGR + PE and control group. Placentas with IUGR + PE had the significantly lowest expression of FasL in VT and EC of villi vessels. Expression of Fas did not differ significantly between the study groups. CONCLUSION: Different expression of FasL in placentas from I-IUGR and IUGR + PE suggests that FasL probably has a different role in the etiology of these two syndromes.

Low molecular weight heparin treatment and impact of inherited thrombophilia type in pregnancies with previous adverse outcome.

OBJECTIVE: To assess the impact of low molecular weight heparin (LMWH) treatment in 50 pregnancies of women with inherited thrombophilia and adverse pregnancy outcome (APO) in previous untreated pregnancies. The impact of "Conventional" (FVL, PT, AT, PC, PS) and "Novel" (MTHFR, PAI-1, ACE) thrombophilias on APO was investigated. METHODS: The primary outcomes (PO) were: early and late pregnancy loss (EPL, LPL), preterm birth (PTB) or term birth (TB) compared to the last untreated pregnancies of the same women. Secondary outcomes (SO) were APO in LMWH treated and last untreated pregnancies ended with birth. PO and SO were compared in relation to the thrombophilia type. RESULTS: LMWH decreased EPL and LPL rate and improved TB rate compared with last untreated pregnancies (p < 0.001). There were less PTB (p = 0.019) and no cases of intrauterine fetal death (IUFD) (p = 0.0019) in LWMH-treated pregnancies. The division to Conventional and Novel thrombophilias showed: (a) difference between pregnancy losses and birth rate (p = 0.0069) and (b) no difference in the prevalence of APO in untreated pregnancies ended with birth. CONCLUSIONS: LMWH treatment improves pregnancy outcome in women with inherited thrombophilia and APO in previous pregnancies. Novel thrombophilias have the equal impact on the pregnancy outcome compared to the Conventional thrombophilias.

The importance of antenatal prevention of RhD immunisation in the first pregnancy.

BACKGROUND: The aim of this study was to examine which pregnancies are associated with RhD immunisation and haemolytic disease of foetus and newborn (HDFN) when postnatal RhD prophylaxis is applied. MATERIAL AND METHODS: This retrospective cohort study included pregnancies with RhD immunisation; each of the pregnant women received anti-D immunoglobulin after delivery, miscarriage or invasive antenatal diagnostic procedures. For each pregnancy we analysed the order of pregnancy that caused immunisation as well as the order of the monitored pregnancy and whether the anti-D antibodies caused HDFN. RESULTS: Anti-D antibody was detected in 1.2% of RhD-negative pregnancies. Out of 89 monitored pregnancies, 56 (63%) were immunised by the first pregnancy, 21 (24%) by the second one, and 12 (13%) by subsequent pregnancies. HDFN occurred in 28 cases; 25 of them were the consequence of the immunisation in the first pregnancy. The most severe cases of HDFN, perinatal death (n=2) and intrauterine transfusion (n=7) were consequence of immunisation during the first pregnancy. Significantly more cases of HDFN were caused by immunisation in the first pregnancy than by immunisation in subsequent pregnancies (χ(2)=12, p<0.01). CONCLUSION: RhD immunisation could be reduced in more than half cases by administering anti-D immunoglobulin at the beginning of the third trimester of pregnancy, especially the first pregnancy.

Asymmetrical fetal growth is not associated with altered trophoblast apoptotic activity in idiopathic intrauterine growth retardation.

AIM: To investigate whether there is difference in trophoblast apoptosis between infants with asymmetrical idiopathic intrauterine growth retardation (IUGR) and those with symmetrical fetal growth appropriate for gestational age (AGA). METHODS: Data and placentas from 52 singleton term pregnancies with idiopathic IUGR, from which a subgroup of 33 (63.4%) infants with asymmetrical growth and malnutrition was identified using the ponderal index served as a study group. The control group included 60 (86.9%) infants with symmetrical growth, identified by the same criterion among 69 normal singleton pregnancies with AGA. IUGR was defined by birthweight less than the 10th percentile of standard values. Ponderal index value was considered as the measurement of fetal growth proportionality. RESULTS: The proportion of fetal thinness up to ponderal index value was greater in the IUGR group than control (χ(2) = 9.2; P = 0.002). There was no statistically significant difference in the cytotrophoblast proliferation (t = 0.88; P = 0.373), trophoblast expression of the Bcl-2 anti-apoptotic factor (z = 0.66; P = 0.505), total trophoblast apoptotic index (t = 0.45; P = 0.651), as in cytotrophoblast (t = 0.01; P = 0.988) and syncytiotrophoblast apoptotic index (t = 0.34; P = 0.730) between the idiopathic asymmetrical IUGR and control group. CONCLUSION: Asymmetry of fetal growth is a result of rather long-term placental nutritive insufficiency in which trophoblasts have a central role. Although being crucial for its functioning, the proliferative and apoptotic trophoblast activity remains unaltered in the placentas from pregnancies with idiopathic IUGR and asymmetrical fetal growth. The results obtained in this study indicate that placental nutritive insufficiency may develop without any deviation in the physiological trophoblast regeneration via apoptosis.

Is there difference in perinatal outcome of singleton and twin pregnancies after assisted conception: two-year experience.

The aim of the study was to compare perinatal outcome of singleton and twin pregnancies conceived after assisted reproductive technologies (ART). This retrospective study included singleton and twin pregnancies conceived after ART in the period from January 1, 2007 until December 31, 2008. The study variables were maternal age (years), parity, body mass index (BMI; kg/m2), week (< or =36 (6/7) and > or = 37) and mode of delivery (vaginal and cesarean section), birth weight (grams) and APGAR score (< or = 7; 8-10). During the study period, there were 195 pregnancies after ART that fulfilled inclusion criteria. We found no between-group difference in parity (chi2 = 0.0133; P = 0.9081), but such difference was found in mean age (t = 2.0486; P = 0.0419) and BMI (chi2 = 31.038; P = 0.001). A statistically significant difference was recorded in preterm delivery rate (chi2 = 25.539; P = 0.001), average duration of pregnancy (t = 12.8591; P = 0.001), average birth weight (t = 10.5446; P = 0.001) and mode of delivery (chi2 = 13,691; P = 0.001). A statistically significant difference was found in low birth weight babies (chi2 = 102.02; P = 0.001) and APGAR score (chi2 = 19.96; P = 0.001), but there was no difference in the prevalence of small for gestational age babies (chi2 = 0.90629; P = 0.635). In conclusion, this study indicated the perinatal outcome after ART to be considerably poorer in twins than in singletons.

Expression of inflammatory cytokines in placentas from pregnancies complicated with preeclampsia and HELLP syndrome.

OBJECTIVE: To investigate the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in villous trophoblast, syncytial knots and decidua placentas from pregnancies complicated with preeclampsia (PE), Hemolysis, Elevated Liver enzymes and Low Platelet count (HELLP) syndrome and gestational age-matched controls. METHODS: Study group included 35 placentas from pregnancies complicated with PE and 35 placentas from pregnancies with HELLP syndrome. Control group included 35 placentas from idiopathic preterm labor. Placentas were matched according to the gestational age. Expression of TNF-α, IL-6 and IL-10 was determined by immunohistochemistry and semi-quantitative HSCORE method in villous trophoblast, syncytial knots and decidua. Non-parametric statistics were used for analyses. RESULTS: There was no difference in the expression of TNF-α, IL-6 and IL-10 in all the studied placental segments between PE, HELLP and gestational age-matched control group. TNF-α (F = 32, 41, p < 0.001), IL-6 (F = 58, 53, p < 0.001) and IL-10 (F = 17, 62, p < 0.001) expression was significantly different in different placental cell types, the highest expression of cytokines was in decidua. CONCLUSION: There was no difference in cytokine expression in villous trophoblast, syncytial knots and decidua among the studied placental groups. The expression of cytokines was highest in decidua in all the studied placental groups.

Maternal pre-pregnancy underweight and fetal growth in relation to institute of medicine recommendations for gestational weight gain.

PURPOSE: Maternal nutritional status is one of the most important factors of fetal growth and development. Consequently, the currently increasing prevalence of underweight women worldwide has come in the focus of interest of perinatal medicine. The aim of the study was to assess the effect of low pre-pregnancy body mass index (BMI) on fetal growth. MATERIALS AND METHODS: Data on 4678 pregnant women and their neonates were retrospectively analyzed. Pre-pregnancy BMI of study women was categorized according to the WHO standards. Fetal growth was assessed by birth weight and birth length, birth weight for gestational age, and ponderal index. RESULTS: Study group included 351 (7.6%) women with pregestational BMI<18.5kg/m(2), while all women with pregestational BMI 18.5-25kg/m(2) (n=3688; 78.8%) served as a control group. The mean birth weight and birth length of neonates born to underweight mothers were by 167g and 0.8cm lower in comparison with the neonates born to mothers of normal nutritional status, respectively (P<0.001 both). The prevalence of small for gestational age (SGA) births was twofold that found in the control group of mothers of normal nutritional status (9.7% vs. 4.9%; P<0.001). The inappropriately low gestational weight gain additionally increased the rate of SGA infants in the group of mothers with low pre-pregnancy BMI (21.4% vs. 10.4%; P=0.02). Pre-pregnancy BMI category did not influence neonatal growth symmetry. CONCLUSION: Low maternal pregestational BMI is associated with fetal growth assessment. Improvement of the maternal nutritional status before pregnancy can increase the likelihood of perinatal outcome.

Apoptosis, proliferation and Fas ligand expression in placental trophoblast from pregnancies complicated by HELLP syndrome or pre-eclampsia.

OBJECTIVE: To investigate apoptosis, proliferation and Fas ligand expression of placental trophoblast in the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and in pre-eclampsia (PE), and to compare this with normal pregnancies. DESIGN: Prospective study. SETTING: University hospital in Croatia. SAMPLE: Placentae from women with HELLP syndrome (n=10), PE (n=10) and normal pregnancies (n=10). METHODS: The HELLP syndrome was diagnosed with platelets <100×10(9) /L, aspartate aminotransferase (AST) and alanine transaminase (ALT) >70 U/L and lactic acid dehydrogenase (LDH) > 600 U/L. Pre-eclampsia was diagnosed at blood pressure >140/90 mmHg, with proteinuria >300 mg/L/24 hours. For detection of apoptosis and proliferation in villous trophoblast, antibodies M30 and Ki-67 were used. Expression of Fas ligand was assessed using immunohistochemistry and the semiquantitative HSCORE method. MAIN OUTCOME MEASURES: Apoptosis, proliferation and Fas ligand expression in villous trophoblast. RESULTS: Apoptosis, proliferation and Fas ligand expression were higher in villous trophoblast in HELLP syndrome than in the PE group (p=0.015, p=0.018 and p=0.002, respectively) and the control group (p=0.000, p=0.012 and p=0.049, respectively). Placentae from the PE group had higher levels of apoptosis (p=0.019), lower Fas ligand expression (p=0.029) and no difference in proliferation (p=0.887) compared with the control group. CONCLUSIONS: There is an increase in apoptosis, proliferation and Fas ligand expression in placentae from women with HELLP syndrome compared with placentae from PE and normal pregnancies. Our findings indicate the possibility of differential mechanisms behind HELLP syndrome and PE.

Trophoblast apoptosis in human term placentas from pregnancies complicated with idiopathic intrauterine growth retardation.

OBJECTIVE: To investigate proliferative, apoptotic, and antiapoptotic activity of placental trophoblast in pregnancies complicated with idiopathic intrauterine growth retardation (IUGR). METHODS: Study group included data and placentas from 52 normal singleton term pregnancies with idiopathic IUGR. Records and placentas from 69 singleton pregnancies with normal fetal growth served as a control group. IUGR was defined by birth weight less than 10th percentile of standard values. Children with congenital malformations and those born with the signs of hypoxia, laboratory or clinical signs of preeclampsia or infection, children born to anemic mothers and those born from pregnancies with an increased coagulation system activity were excluded. RESULTS: There was no statistically significant difference in the cytotrophoblast proliferation index value (Z = 0.24; P = 0.553), trophoblast expression of the Bcl-2 antiapoptotic factor (Z = 0.47; P = 0.634), and trophoblast apoptotic index (Z = 0.51; P = 0.613) between the idiopathic IUGR and control group. CONCLUSION: The proliferative and apoptotic events in the trophoblast of placentas with idiopathic IUGR did not differ from physiologic ones. Study results suggest the IUGR syndrome to have no uniform etiology or even underlying pathophysiology that would determine the possible fetal risk and subsequent long-term consequences for fetal health and life. This imposes the need of a more precise definition and unambiguous distinction between the idiopathic and other forms of IUGR.

Morphological characteristics of placentas associated with idiopathic intrauterine growth retardation: a clinicopathologic study.

OBJECTIVES: To investigate histopathologic findings, placental diameters and characteristics of syncytial knots in the placentas from idiopathic intrauterine growth retardation (IUGR) pregnancies, and to compare them with a normal birth weight group. STUDY DESIGN: Based on strict eligibility criteria, this prospective case-control study included 52 term placentas from idiopathic IUGR pregnancies and 69 term placentas from normal birth weight pregnancies. The study was carried out at the Clinical Hospital Centre, Split, where all placentas were collected and examined. For each placenta, diameters were measured and the following histopathologic findings were recorded: infarction, intervillous thrombosis, abruption, villous branching and maturation, chorioamnionitis, decidual vasculopathy and hemorrhagic endovasculitis for each placenta. In addition we assessed quantitative (number of syncytial knots and number of syncytial nuclei per syncytial knot) and qualitative (density and surface area) characteristics of syncytial knots in each placental sample. Statistical significance was tested using chi(2)-test, Student's t-test and Mann-Whitney U-test. Statistical significance was set at P< or =0.05. RESULTS: There was no difference in investigated histopathologic findings between idiopathic IUGR placentas and control group placentas. Placental diameters correlated significantly with neonatal birth weight (r=0.64; P<0.01); with higher birth weight there is an increase in placental diameters. Syncytial knots from idiopathic IUGR had significantly smaller surface area (Z=2.637; P=0.008) and higher density (Z=3.225; P=0.001) compared with the control group, while there is no difference in number of syncytial knots per individual villus, total number of syncytial knots in each placenta sample or number of syncytial nuclei per syncytial knot. CONCLUSIONS: The investigated histopathologic findings in idiopathic IUGR placentas are incidental, with no higher frequency than in placentas from uncomplicated pregnancies, and should not be considered as possible causative factors for idiopathic IUGR. The demonstrated qualitative changes of syncytial knots in placentas associated with IUGR could represent a compensatory mechanism.

Influence of growth and transcriptional factors, and signaling molecules on early human pituitary development.

Development and differentiation of the human pituitary gland was investigated in 6 human conceptuses 6-9 postovulatory weeks old, using immunohistochemical technique to investigate appearance of different developmental factors, and immunofluorescent double staining technique with Ki-67 to investigate proliferation. In the developing human pituitary gland, different developmental factors appeared in temporally and spatially restricted patterns, thus contributing to formation of different parts of the gland: adenohypophysis, neurohypophysis and associated mesenchyme. Some growth factors were not primarily involved in cell proliferation (TGF-ss, BMP-2/4 and GATA), but in differentiation of pituitary cells: TGF-ss, BMP-2/4 and GATA probably contributed to differentiation of cells in the mesenchyme at earlier stages, while their influence on differentiation of specific cell types in the adenohypophysis increased with development. At later developmental stages, those factors also influenced the differentiation of cells in the neurohypophysis. FGF-8 and FGF-10 probably participated both in the growth and differentiation of pituitary cells: while FGF-8 could act during early developmental stages, FGF-10 participated in the same processes at later stages of pituitary development. Expression of EGF and VEGF indicated their involvement in proliferation of initially differentiated pituitary cells, and in subsequent differentiation of some cell types in the adenohypophysis and neurohypophysis. In the mesenchyme, expression of VEGF might be related to formation of new blood vessels as well. Precise patterns of appearance of growth and transcription factors, and signaling molecules in developing human pituitary gland seem to be important for cell proliferation, differentiation, and normal morphogenesis of the gland.