Placental angiopoietin-1 and angiopoietin-2 expression and correlation with birth weight in twins.

OBJECTIVE: To study the expression of angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2) in human placentas of dizygotic dichorionic twins in relation to fetal growth. STUDY DESIGN: Placentas from dizygotic-dichorionic twins (n=14) obtained from normal uncomplicated pregnancies were collected immediately after delivery. A quantitative assessment of the placental expression of Ang1 and Ang2 was done using quantitative PCR. Birth weight and anthropometric parameters were measured. Statistical analysis was preformed. RESULTS: Ang1 and Ang2 were expressed in the placentas. We found a significant positive correlation between birth weight and expression of both Ang1 and Ang2 (p<0.009, p<0.011, respectively). In addition, there was a significant positive correlation between skin fold, BMI and Ang1 expression (p<0.0001 and p<0.01, respectively). CONCLUSION: A positive correlation between twin birth weight and placental angiogenesis was found. We suggest that placental expression of Ang1 and Ang2 may have an important role in fetal growth in twin pregnancy.     

Study on the expression of angiotensin II (ANG II) receptor subtype 1 (AT1R) in the placenta of pregnancy-induced hypertension

OBJECTIVE: To study the expression of angiotensin II (ANG II) receptor subtype 1 (AT(1)R) in the human placenta with pregnancy-induced hypertension (PIH). METHODS: Immunohistochemistry was used to detect the expression of AT(1)R in placental tissues of 30 patients with PIH and 10 patients with normal pregnancies (control group). The PIH tissues were further divided into 3 groups: mild PIH group, moderate PIH group and severe PIH group. Each group consisted of 10 patients. A high-resolution pathological image analysis system (HPIAS-1000) was used to determine the quantity of AT(1)R expression. RESULTS: The integral optical density and area of staining in the syncytiotrophoblast (STB) layer and villous endothelium of the placenta were significantly increased in PIH patients, in the moderate and severe PIH groups, as compared with the control group (P < 0.05), indicating that the expression of AT(1)R was highly increased in PIH. However, there was no significant difference between normal pregnancy and the mild PIH group (P > 0.05). Furthermore, statistically significant differences in AT(1)R expression were observed between mild, moderate and severe PIH groups (P < 0.05). CONCLUSION: The expression of AT(1)R is statistically significantly increased in the STB layer and villous endothelium of human placenta with PIH. Expression increases with the severity of the disease. Increased expression may be involved in the pathogenesis of PIH.     

表皮生长因子及其受体与胎儿出生体重的关系

目的探讨表皮生长因子（ＥＧＦ）及其受体与胎儿出生体重的关系。方法采用酶联免疫吸附测定法对正常非孕妇女１５例（对照组）、足月正常体重儿４０例（正常体重儿组）、ＩＵＧＲ儿４０例（ＩＵＧＲ儿组）、巨大儿２５例（巨大儿组）的母血清、脐血清及羊水中ＥＧＦ浓度进行测定,同时采用免疫组化方法对以上各组胎盘及胎膜上ＥＧＦ受体（ＥＧＦＲ）进行测定。结果各组母血、脐血及羊水中ＥＧＦ浓度明显高于对照组（Ｐ＜００５）。ＩＵＧＲ儿组母血、脐血及羊水中ＥＧＦ浓度低于正常体重儿组,差异有显著性。巨大儿组母血、脐血及羊水中ＥＧＦ浓度与正常体重儿组比较,差异无显著性。在ＩＵＧＲ儿组胎盘及胎膜上ＥＧＦＲ表达明显低于正常体重儿组（Ｐ＜０．０１）,巨大儿组胎盘上ＥＧＦＲ表达高于正常体重儿组。结论ＥＧＦ及其受体与ＩＵＧＲ的发生有关,在妊娠后期测定母血及羊水中ＥＧＦ浓度,对评价胎儿的生长发育具有重要意义。     

Placental cord insertion and birth weight discordancy in twin gestations

OBJECTIVE: To evaluate whether abnormal umbilical cord insertion (UCI) into the placenta is a risk factor for birth weight discordancy in twin gestations.METHODS: Pathology records of all liveborn twins delivered between January 1993 and June 1996 were reviewed. The information collected included gestational age at delivery, birth weight, gross placental pathology, and placental UCI-velamentous, marginal, or disc. Discordancy in birth weight was defined as an intrapair difference of at least 20%. Analyses were stratified on placental chorionicity. Odds ratios and 95% confidence intervals for birth weight discordancy were calculated based on the presence of an abnormal (velamentous or marginal) placental UCI relative to normal (disc) UCI on both placentae, after adjusting for potential confounders. RESULTS: There were 447 twin pairs identified. Dichorionic diamniotic placentation was present in 358 pairs (80.1%), monochorionic diamniotic in 84 (18.8%), and monochorionic monoamniotic in five (1.1%). There was a 13-fold increase in the risk of birth weight discordancy in monochorionic diamniotic twins in the presence of a velamentous UCI (odds ratio 13.5, 95% confidence interval 1.4, 138.4), with a rate of birth weight discordancy of 46%. This relationship was not demonstrated in dichorionic diamniotic twins (odds ratio 1.0, 95% confidence interval 0.3, 3.5). CONCLUSION: Birth weight discordancy in twins is a different entity depending on chorionicity. The substantial increase in birth weight discordancy in monochorionic diamniotic twins that accompanies velamentous UCI underscores the need for prenatal detection and increased surveillance in these twins.     

Platelet angiotensin II binding sites in normotensive and hypertensive women

Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10(9) cells) when compared with the non-pregnant women (9.0 fmol/10(9) cells P less than 0.001). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10(9) cells) when compared with the 25 normotensive pregnant women (P less than 0.001). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10(9) cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10(9) cells) although the difference was not statistically significant (P less than 0.04). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy.     

Platelet angiotensin II binding sites in normotensive and hypertensive women

Summary. Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10⁹ cells) when compared with the non-pregnant women (9.0 fmol/10⁹ cells   P <0.001  ). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10⁹ cells) when compared with the 25 normotensive pregnant women (   P <0.001  ). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10⁹ cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10⁹ cells) although the difference was not statistically significant (   P <0.04  ). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy.     

Angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor (AT1R) gene polymorphism and its association with preeclampsia in Chinese women.

OBJECTIVE: To investigate whether polymorphisms of angiotensin converting enzyme gene (ACE) and angiotensin II receptor type 1 gene (AT1R) are associated with etiology of preeclampsia and renal impact in women with preeclampsia. METHODS: DNA was extracted from peripheral blood of 133 patients with preeclampsia and 105 healthy pregnant women. The I/D polymorphism of the ACE gene was assessed by polymerase chain reaction, and the A1166C polymorphism of the AT(1)R gene was additionally assessed by DdeI digestion. The level of proteinuria, fasting serum urea, creatinine and uric acid were investigated according to different genotypes of ACE and AT1R genes. RESULTS: The frequency of genotypes of the ACE gene and the AT1R gene was similar in preeclampsia and normal pregnancy. DD and ID genotype predominated in patients with severe proteinuria, as well as increased serum urea and uric acid. Serum creatinine was also increased, but no significant difference was found among three genotypes. The level of proteinuria, serum uric acid, urea, and creatinine did not vary between different AT1R genotypes. Compared with patients without renal dysfunction, the frequency of DD and ID genotypes of ACE gene was much higher in those with renal dysfunction, but AC and CC genotypes of AT1R gene were not. CONCLUSION: We found no association of the two gene polymorphisms with preeclampsia. However, ACE gene I/D polymorphisms were associated with the severe proteinuria and renal dysfunction seen in preeclampsia. Preeclampsia patients carrying the D allele may be susceptible to renal dysfunction.     

Placental weight and neurologic outcome in the infant: a review

Objective: To review the agreement of published standards on placental weights (PW) and fetal–placental (F/P) ratios, examine factors contributing to PW and ask whether aberrant placental weight is associated with adverse neurologic outcome. Methods: We conducted a literature search for standards of PW, F/P ratio and the relationship of PW to perinatal death, neonatal encephalopathy or cerebral palsy. We reviewed 17 studies of normative PW and 10 of F/P ratios. Since 1990, seven studies compared mean and extreme percentile bounds between 35 and 42 weeks of gestation. Nine publications examined PW and neurologic outcome. Results: Untrimmed placentas were heavier by 131–193 g. F/P ratios differed by 0.2–2.34 between trimmed and untrimmed placentas. Fresh, frozen or fixed preparation prior to weighing had minimal effect on weight. Gender and race had negligible affect. Placentas from caesarean sections averaged 75 g heavier than vaginal deliveries. There were no consistent associations of aberrant PW and neurologic outcome. Conclusions: Reference standards of recent studies on trimmed placentas were largely in agreement. Current findings relating aberrant PW and adverse neurologic outcome are inconclusive. Further study of the relationship between placental weight and neonatal encephalopathy or cerebral palsy is warranted, in representative populations using within-study controls.     

Placental aminopeptidase A as a possible barrier of angiotensin II between mother and fetus

Aminopeptidase A (AP-A EC 3.4.11.7), which is a membrane-bound zinc metalloprotease, is present in the placenta. AP-A selectively hydrolyzes N-terminal glutamyl and aspartyl residues and cleaves angiotensin II to form angiotensin III. To determine the role of placental aminopeptidase A under physiological and pathological conditions, we evaluated its immunolocalization and enzymatic activities in the placenta. AP-A was localized in the basal zone of the syncytiotrophoblast, in the membranes of the cytotrophoblast, and in fetal arterioles and venules within the stem villi. AP-A activity in the microsomal fraction of placental villi seemed to be remained essentially constant throughout gestation. The renin-angiotensin system is considered to be accelerated in pre-eclampsia. This AP-A activity was higher in pre-eclampsia (2.86+/-0.30 nmol beta NA/mg protein/h) than in uncomplicated pregnancy from 28 to 41 weeks of gestation (2.08+/-0.18 nmol beta NA/mg protein/h). Angiotensin II evoked AP-A activity in first trimester trophoblast, and Losartan and PD 123177 in combination significantly inhibited this induction of AP-A activity. The results of immunohistochemical evaluation and enzymatic activity suggested that placental aminopeptidase A may play a role as a component of the barrier of angiotensin II between mother and fetus.     

Correlation between maternal first trimester plasma leptin levels and birth weight among normotensive and preeclamptic women

Objective.?To determine the connection between maternal first trimester serum leptin levels and newborn weight.

Methods.?The study included 37 preeclamptic women and 53 normotensive women who considered the control group. Maternal blood samples were withdrawn at 13 weeks of gestation for the measurement of leptin concentrations. Birth weights were transformed to z-scores according to maternal and obstetrical features, based on customised centiles. Non-parametric tests, student's t-test, Pearson's correlation, Spearman's correlation and linear regression analysis were performed in our analysis.

Results.?Pre-pregnancy body mass index and first trimester maternal plasma leptin levels were significantly higher among women with preeclampsia (p?=?0.015 and p?<?0.001, respectively). Birth weight z-score was negatively correlated with leptin levels (r?=??0.570, p?<?0.001), in preeclamptic group and in control group (r?=??0.477, p?<?0.001). The regression modelling demonstrated a significant negative association between birth weight z-scores and leptin for both groups.

Conclusion.?Maternal first trimester serum leptin demonstrates a significant negative association with neonatal weight in preeclamptic pregnancies and to a lesser extent in normotensive pregnancies. A possible leptin's involvement in pathophysiological adaptations that define the foetal growth potential can be supported.     

Placental function studies in low birth weight infants with and without dysmaturity

Maternal blood levels of human placental lactogen and schwangerschaftsprotein 1 were measured in 51 women who delivered a growth-retarded infant. The levels were substantially lower in the 27 women whose infants were clinically dysmature than in the 24 women whose infants were small but of normal appearance. About one-half (44%) the cases of true dysmaturity had abnormal concentrations of human placental lactogen (less than 4 mg/L), whereas none of the small but normal group had values in this zone. It is concluded that biochemical tests of this type reflect dynamic aspects of placental function and not simply the overall size of the fetus and placenta.     

Gestational therapy with an angiotensin II receptor antagonist and transient renal failure in a premature infant

The fetotoxic effects of angiotensin converting enzyme inhibitors when used during the second half of pregnancy are well known. The more recently developed angiotensin II receptor antagonists appear to yield similar fetal abnormalities. We report a premature infant born to a 41-year-old mother with a long history of infertility who had received losartan therapy for hypertension throughout an undetected pregnancy. Ultrasound examination 2 days prior to delivery identified a single fetus at 29 weeks gestation, anhydramnios, and an empty fetal bladder. The neonatal course was complicated by oliguria, hyperkalemia, marked renal dysfunction, respiratory failure, joint contractures, and a large anterior fontanelle with widely separated sutures. Hypotension (mean arterial pressure<25 torr) on day 1 responded to volume expansion, dopamine, and hydrocortisone. Serum creatinine reached a maximum of 2.7 mg/dL on day 6 and decreased to 0.4 by day 56. No formal urinalysis was performed, but the urine was reported to be visually clear throughout the course. Although a renal ultrasound on day 2 was normal, a follow-up study at 7 months revealed bilateral generalized parenchymal echogenicity, consistent with medical renal disease. Since then, weight and length have been at the 5th percentile or less, with apparent renal tubular acidosis necessitating the addition of sodium citrate supplements. This case emphasizes the importance of maintaining a high index of suspicion for potential pregnancy when contemplating the use of a drug of this class, and considering serial testing for pregnancy when using such drugs, even in patients with a longstanding history of infertility.     

Positive correlation between the quantity of Wharton's jelly in the umbilical cord and birth weight

ObjectiveTo determine the possible protective effects of Wharton’s jelly (WJ) in umbilical cord and fetal growth by investigating the relationship between the amount of WJ and fetal birth weight.Materials and MethodsThis study enrolled 299 women who delivered after an uneventful pregnancy. After separation of the placenta, a 5 cm long section of umbilical cord was removed by scalpel. The weight of the cord section; the weight, volume, and density of its WJ; and the weight of the newborn and placenta were measured.ResultsA significant positive correlation was found between WJ quantity, birth weight (p = 0.002), and placental weight (p = 0.003), whereas a significant negative correlation was observed for WJ density, fetal growth (p = 0.035), and placental growth (p = 0.002). WJ density was 1.63 ± 0.27 g/mL. No significant correlation was found between the amount of WJ and weight gained during pregnancy (p = 0.274) or maternal age (p = 0.220).ConclusionAs the amount of WJ increases, fetal weight increases. Accordingly, the amount of WJ might be a factor that influences fetal growth.     

Placental share and hemoglobin level in relation to birth weight in twin anemia-polycythemia sequence

IntroductionTwin anemia-polycythemia sequence (TAPS) is a newly described form of chronic twin transfusion. Previous observational studies noted a discordance between birth weight and individual placental share in TAPS. The purpose of this study was to investigate if fetal growth in monochorionic (MC) twins with TAPS is determined by placental share or by the net inter-twin blood transfusion.MethodsAll consecutive MC twin placentas of live-born twin pairs with and without TAPS examined at our center between June 2002 and February 2014 were included in this study. Hemoglobin (Hb) levels and individual placental share were evaluated at birth and correlated with birth weight share. We excluded MC twin pregnancies with twin–twin transfusion syndrome.ResultsA total of 270 MC twin pregnancies (TAPS group, n = 20; control group without TAPS, n = 250) were included in this study. Donors with TAPS had a lower birth weight than recipients in 90% (18/20) of cases, but a larger placental share in 65% (13/20) of cases. In the TAPS group, birth weight share was positively correlated with Hb share at birth (P < 0.01) but not with placental share (P = 0.54). In the control group without TAPS, birth weight share was strongly correlated with placental share (P < 0.01) but not with Hb share (P = 0.14).DiscussionA relatively larger placental share may enable the survival of the anemic twin in TAPS.ConclusionIn contrast with uncomplicated MC twins, fetal growth in MC twins with TAPS is determined primarily by the net inter-twin blood transfusion instead of placental share.