Uncomplicated Pregnancy Group Research Articles

The impact of maternal intrahepatic cholestasis during pregnancy on the growth trajectory of offspring: a population-based nested case‒control cohort study

BackgroundIntrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring.MethodOur case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics.ResultMaternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P < 0.05). However, no significant differences in LAZ, weight-for-length z score (WLZ), BMI-for-age z score (BAZ), or HCZ were observed between groups in the 13- to 36-month age range. Maternal maximum lactate dehydrogenase (LDH) and total bile acids (TBA) levels during pregnancy were inversely correlated with LAZ and WAZ in the first year. Furthermore, offspring of mothers with ICP exhibited a greater incidence of stunting (24% vs. 6.9%, P = 0.004) and abnormal HCZ (14% vs. 3.7%, P = 0.034).ConclusionsGrowth disparities in offspring of ICP-affected pregnancies were most significant within the 1- to 12-month age range. During this period, maximum maternal LDH and TBA levels were negatively correlated with LAZ and WAZ values of offspring. The observation of similar growth rates between ICP and control group offspring from 13 to 36 months suggested catch-up growth in the ICP group.

Gestational diabetes mellitus and cardio-metabolic risk factors in women and children at 3 years postpartum

IntroductionGestational diabetes mellitus (GDM) is thought to be associated with cardio-metabolic risk factor development in women and their children during the early postpartum period and early childhood. We hypothesized that these women and their children would exhibit increased abnormal cardio-metabolic risk factors three years after pregnancy.MethodsWomen from the Screening Tests to Predict Poor Outcomes of Pregnancy study were invited to attend a follow-up with the child from their index pregnancy at 3 years postpartum. Women and children were assessed for anthropometric measures and haemodynamic function. Fasting blood samples were obtained from women to assess lipid and glucose status.ResultsA total of 281 woman-child dyads participated in the 3-year follow-up, with 40 women developing GDM during their index pregnancy. Fasting serum insulin was higher in women with GDM in index pregnancy compared to those with an uncomplicated pregnancy. However, this association was mediated by early pregnancy BMI and socioeconomic index (SEI). The rate of metabolic syndrome was higher in the GDM group than the uncomplicated pregnancy group. Maternal GDM was associated with elevated maternal fasting serum triglycerides at 3 years after adjustment for early pregnancy BMI and SEI. Children exposed to GDM in utero had higher waist circumference compared to children born after an uncomplicated pregnancy, but this is mediated the above covariates.ConclusionExposure to GDM is associated with elevated serum triglycerides in women at 3 years postpartum but other cardiometabolic outcomes in women and children appear to be mediated by early pregnancy BMI and SEI.

Abstract P170: Cardiovascular-related Pregnancy Complications: Associations With Health Behaviors And Mental Health During The Covid-19 Pandemic

Pregnancies with cardiovascular (CV) complications are more likely to involve additional complications, poorer short and long-term health, and worse fetal outcomes. Additionally, CV complications are associated with poorer mental health, lower socioeconomic status, and non-White race/ethnicity. The COVID-19 pandemic has had negative effects on mental well-being and disproportionately affects people of lower socioeconomic status and non-White race/ethnicity. Thus, we hypothesized that the pandemic would differentially affect pregnant people with and without CV complications. We performed a cross-sectional survey of 465 pregnant people in California from June 6 through July 29, 2020. Twenty-three participants reported CV complications (e.g., hypertensive disorders, gestational diabetes) and 29 participants reported non-CV complications. The CV group was 56.5% (13 of 23) Latinx and 43.5% (10 of 23) White versus the uncomplicated pregnancy group, which was 33.7% (137 of 407) Latinx and 66.3% (270 of 407) White (chi-square, p=0.03; 6 respondents did not answer). The CV complications group was 9.5% (2 of 21) African American and the uncomplicated pregnancy group was 4.9% (19 of 392) African American (Fisher’s Exact, p=0.053; 23 respondents did not answer). We assessed 64 health behaviors reported on a Likert scale with the Wilcoxon 2-Sample Test and found the CV group reported more health-promoting behaviors, including: less likely to eat sweets (p=0.004), more likely to sanitize frequently used areas in their homes and their groceries (p=0.049 and 0.069, respectively). However, they were also more likely to smoke cigarettes (p=0.02). While the two groups did not differ significantly on stress, depression, or anxiety, the CV group was more likely to worry that their babies may be hospitalized after birth (p=0.01) and their provider may be unavailable during delivery (p=0.047). Concerns for self and baby trended towards significance for the CV group, which reported being more likely to worry about getting sick (p=0.077) and their babies being born early (p=0.079) or getting sick (p=0.098). While preliminary, these data suggest that COVID-19 disproportionately affects pregnant people with prenatal CV complications. Given limited research on pregnancy during COVID-19 and the primary focus on biological outcomes, these findings indicate a clear need to address the pandemic’s influence on behavioral and emotional health during pregnancy - especially for those with CV complications who are at higher risk of poor maternal and fetal outcomes.

Biomarkers and Their Relation to Cardiac Function Late After Peripartum Cardiomyopathy

BackgroundAngiogenic imbalance involving the placental protein soluble Fms-like tyrosine kinase-1 (sFlt-1) and cleavage of the nursing-hormone prolactin by the enzyme cathepsin D (CD) both play a role in the pathogenesis of peripartum cardiomyopathy (PPCM). We hypothesized that angiogenic imbalance and increased activity of CD have a long-lasting impact in women with PPCM. Methods and ResultsA nationwide Danish cohort of women with PPCM (PPCM group, n = 28), age matched women with previous preeclampsia (n = 28) and uncomplicated pregnancies (n = 28) participated in a follow-up study including biomarker analysis, exercise testing and cardiac magnetic resonance imaging. The median time to follow-up was 91 months (range 27–137 months) for the PPCM group. Levels of sFlt-1, placental growth factor, N-terminal pro-natriuretic brain peptide, and copeptin were all significantly higher in the PPCM group. More women in the PPCM group had detectable CD activity (68%) compared with the preeclampsia group (29%) and uncomplicated pregnancies group (36%) (P = .0002). Levels of angiogenic factors and biomarkers correlated inversely with maximal exercise capacity and cardiac functional parameters assessed with cardiac magnetic resonance imaging. ConclusionsWomen with PPCM had higher biomarker levels and CD activity up to 7 years after diagnosis. Higher biomarker levels correlated inversely with maximal exercise capacity and markers of cardiac dysfunction suggesting that persistent angiogenic imbalance and increased CD activity is associated with residual cardiac dysfunction.

Assessment of renal volume by 3D VOCAL Ultrasonography method in late-onset growth-restricted fetuses with normal amniotic fluid index.

The aim of this study was to study renal volumetric alterations and renal artery doppler changes in late-onset fetal growth restricted (FGR) fetuses with normal amniotic fluid compared to healthy pregnancies. This prospective study was composed of pregnant women with late-onset FGR and a control group of uncomplicated pregnancies within 32-37 weeks of gestation. Following the assessment of umbilical, bilateral uterine, middle cerebral using Doppler Ultrasonography (US), three dimensional (3D) US Virtual Organ Computer-aided Analysis (VOCAL) was executed to calculate bilateral renal volumes. A total of 76 fetuses with FGR and 51 healthy fetuses (control group) were evaluated. Umbilical artery Doppler systole/diastole and Pulsatility index values were found to be significantly different between the two groups (p = 0.001 and p = 0.001, respectively). Middle cerebral, bilateral uterine, and bilateral renal arteries' Doppler indices revealed no difference between the two groups. Right, left, and mean renal volume of the fetuses with FGR were smaller than the control group, and the differences were statistically significant (p = 0.025, p = 0.004, p = 0.004, respectively). Left renal volume was significantly greater than the right renal volume in the control group (p = 0.009). Although not accompanied by oligohydramnios, and having similar renal vascular resistance as the control group, renal volumes of fetuses with late-onset FGR were still observed lower than the control group. This difference was explained by not decreased blood flow via redistribution but other mechanisms like glomeruli reduction and glomerular apoptosis.

Levels of sex steroid hormones and their receptors in women with preeclampsia

BackgroundPregnant women have high serum concentrations of sex steroid hormones, which are major regulators of paracrine and autocrine responses for many maternal and placental functions. The main purpose of this study was to compare patients with preeclampsia and patients with uncomplicated pregnancies in terms of serum steroid hormones (estradiol [E2], progesterone [P4], dehydroepiandrosterone sulfate [DHEAS], and testosterone [T]) throughout pregnancy and the levels of cord blood and placental steroid receptors during the third trimester.MethodsQuantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry were used to determine the levels of steroid hormones in the serum and cord blood and the placental levels of estrogen receptor-α (ERα), ERβ, androgen receptor (AR), and progesterone receptor (PR).ResultsThere were 45 women in the uncomplicated pregnancy group and 30 women in the preeclampsia group. Serum levels of T were greater and serum levels of E2 were reduced in the preeclampsia group, but the two groups had similar levels of P4 and DHEAS during the third trimester. Cord blood had a decreased level of DHEAS in the preeclampsia group, but the two groups had similar levels of P4, E2, and T. The two groups had similar placental mRNA levels of ERα, ERβ, AR, and PR, but the preeclampsia group had a higher level of ERβ protein and a lower level of ERα protein. Immunohistochemistry indicated that the preeclampsia group had a greater level of ERβ in the nucleus and cytoplasm of syncytiotrophoblasts and stromal cells.ConclusionsWomen with preeclampsia had lower levels of steroid hormones, estrogen, and ERα but higher levels of T and ERβ. These molecules may have roles in the pathogenesis of preeclampsia.

First-trimester placental function in levothyroxine-using pregnant women: a case-control study

We aimed to compare the pregnancy-associated plasma protein-A (PAPP-A) and the uterine artery pulsatility index (UtA PI) levels of euthyroid pregnant women using levothyroxine vs. a control group of uncomplicated pregnancies and to evaluate the effects of different levothyroxine dosages on pregnancy outcomes. We retrospectively evaluated 206 levothyroxine-using pregnant women by looking at their basic placental function markers and obstetric outcomes. A sample of 449 women whose pregnancies concluded with uncomplicated term deliveries composed of our control group. To examine the relationship between the levothyroxine dosages and the frequency of pregnancy complications, levothyroxine users were divided into different groups according to the 75, 100, and 150 mcg cutoffs. The median PAPP-A MoM levels of levothyroxine users were significantly lower at 0.94 vs. 1.11 (p < .001) and the median mean UtA PI was significantly higher than the control group at 2.08 vs. 1.74 (p < .0001). The median birth weight was significantly lower for the levothyroxine users’ group at 3292 g vs. 3427 g (p < .0001). Using 75, 100, and 150 mcg dose cutoffs, PAPP-A MoM, mean UtA PI and obstetric complication frequencies were not significantly different among levothyroxine users. Significant changes in placental function markers have been observed in euthyroid levothyroxine-using pregnant women during the first trimester. However, the frequency of obstetric complications does not appear to be dose dependent.

Long-Term Cardiac Function After Peripartum Cardiomyopathy and Preeclampsia: A Danish Nationwide, Clinical Follow-Up Study Using Maximal Exercise Testing and Cardiac Magnetic Resonance Imaging.

BackgroundLong‐term clinical studies of peripartum cardiomyopathy (PPCM) are few. We aimed to measure the long‐term effect of PPCM on cardiac function in comparison with the long‐term effects of severe preeclampsia and uncomplicated pregnancy.Methods and ResultsA nationwide Danish cohort of women diagnosed with PPCM from 2005 to 2014 (PPCMgroup) were invited to participate in a clinical follow‐up study including maximal cardiopulmonary exercise testing and cardiac magnetic resonance imaging. Matched women with previous severe preeclampsia (preeclampsia group) and previous uncomplicated pregnancies (uncomplicated pregnancies group) served as comparison groups. A total of 84 women with 28 in each group participated. Median time to follow‐up after PPCM was 91 months. Most women (85%) in the PPCM group reported no symptoms of heart failure. Mean left ventricular ejection fraction in the PPCM group was normal at 62%, but significantly lower than in the preeclampsia group and the uncomplicated pregnancies group where mean left ventricular ejection fraction was 69% and 67%, respectively (P<0.0001). Women in the PPCM group also had impaired diastolic function with reduced left ventricular peak filling rate, left atrial passive emptying volume, and left atrial passive emptying fraction. Maximal exercise capacity (peak VO 2) was also reduced in the PPCM group compared with the preeclampsia group and the uncomplicated pregnancies group, and PPCM, high body mass index, and low left ventricular ejection fraction independently predicted reduced peak VO 2. Only 1 woman with PPCM had late gadolinium enhancement.ConclusionsWomen generally recovered left ventricular ejection fraction and were asymptomatic 7 years after PPCM, but had subtle diastolic dysfunction on cardiac magnetic resonance imaging and reduced peak VO 2. Focal myocardial fibrosis assessed with late gadolinium enhancement was, however, uncommon.

Circulating Levels of Pregnancy-Associated, Placenta-Specific microRNAs in Pregnant Women With Placental Abruption.

The aim of this study was to clarify the association between circulating pregnancy-associated, placenta-specific microRNAs (miRNAs) in maternal plasma and placental abruption. All samples were obtained after receiving written informed consent, and the study protocol was approved by the institutional review board. Maternal blood samples (7 mL) were obtained at 25 to 40 weeks of gestation from 15 cases of placental abruption (placental abruption group) and from 24 cases of uncomplicated pregnancies (uncomplicated pregnancy group). The plasma concentrations of pregnancy-associated, placenta-specific miRNAs (miR-515-3p, -517a, -517c, and -518b) were measured by quantitative real-time reverse transcription-polymerase chain reaction. There were no significant differences in clinical characteristics between the 2 groups. The median concentration of plasma cell-free miR-517c in the placental abruption group was 21 672.2 copies/mL, whereas that in the uncomplicated pregnancy group was 13 452.0 copies/mL (Mann-Whitney U test, P = .047). Receiver operating characteristic curve analysis revealed that plasma cell-free miR-517c levels discriminated placental abruption from uncomplicated pregnancy with an area under the curve of 0.692. When a cutoff negative/positive value of 15 669.6 copies/mL was selected, the sensitivity and specificity were 73.3% and 62.5%, respectively. In addition, the positive and negative predictive values were 55.0% and 78.9%, respectively. Plasma cell-free miR-517a and miR-517c levels in the large abruption (degree of abruption ≥50% of placenta) group were significantly higher than in the small abruption (<50%) group ( P = .03 for both miRNAs). In conclusion, the circulating level of cell-free miR-517c in maternal plasma was increased as a consequence of placental abruption and may be a potential biomedical marker for placental abruption.

The obesity associated FTO gene variant and the risk of adverse pregnancy outcomes: Evidence from the SCOPE study.

To investigate whether the FTO rs9939609 single nucleotide polymorphism (SNP), which is a risk factor for obesity and vascular diseases, is also associated with pregnancy complications including pre-eclampsia, gestational hypertension, small for gestational age pregnancy (SGA), and spontaneous preterm birth (sPTB). A case-control study of 1,741 nulliparous Caucasian women, their partners, and infants was conducted. DNA was extracted from peripheral blood or saliva from parents and cord blood from infants and genotyped using the Sequenom MassARRAY system. The prevalence of maternal and infant AA genotype of FTO rs9939609 was increased in the SGA group compared with the uncomplicated pregnancy group (19.2% vs. 13.4%, OR = 1.7, 95% CI = 1.1-2.6, P = 0.02 and 24.6% vs. 12.5%, OR = 2.7, 95% CI = 1.6-4.6, P = 0.0002). The prevalence of maternal and infant AA genotype of FTO rs9939609 was also increased in the sPTB group compared with the uncomplicated pregnancy group (20.8% vs. 13.4%, OR = 2.1, 95% CI = 1.2-3.8, P = 0.009 and 20.0% vs. 12.5%, OR = 2.4, 95% CI = 1.0-5.3, P = 0.03). The maternal and infant AA genotype of the obesity associated FTO rs9939609 SNP associates with increased risk for SGA and sPTB. This SNP may be important in predicting the risk of these pregnancy complications and subsequent vascular diseases.

O114. Maternal cardiovascular changes in pregnancies complicated by small for gestational age neonate with or without maternal hypertension

Objective The literature describing the maternal cardiovascular changes in pregnancies complicated by fetal growth restriction and maternal hypertension is limited, conflicting and does not discriminate the two pathologies. The aim of this study was to investigate maternal cardiovascular changes in pregnancies complicated by small for gestational age (SGA) neonates with or without maternal hypertension. Methods This was a prospective case-control study including pregnancies resulted in SGA neonate (n = 159) and a group of uncomplicated pregnancies (n = 473), recruited after 20 weeks’ gestation. The SGA group was further divided according to fetal Doppler to define fetal growth restriction (FGR; n = 51) and maternal hypertension (n = 51). FGR was defined as estimated fetal weight below the 10th centile with abnormal umbilical artery Doppler (pulsatility index [PI] above the 90th centile or absent or reversed end-diastolic flow). Maternal cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI) were recorded using the USCOM®, while the augmentation index (AIx) was assessed using the Arteriograph®.Uterine artery (UtA) mean PI was assessed at the same visit. Mann–Whitney test and regression analysis were used for statistical analysis. Results Compared to controls, the SGA pregnancies had significantly lower CO (median 6.08 L/min, IQR 5.31–6.86 vs 6.65 L/min, IQR 5.68–7.79, p = 0.006), but significantly higher SVR (median 1091 dynes-sec/cm5, IQR 998–1359 vs 1040 dynes-sec/cm5, IQR 878–1263, p = 0.008). Both AIx and UtA mean PI were significantly higher in the SGA pregnancies compared to controls (p = 0.002 and p 0.001, respectively). In normotensive SGA, the results were similar (p 0.05). However, after correcting for body surface area, neither cardiac index nor SVR index were significantly different between the two study groups (p = 0.209 and p = 0.139, respectively). In normotensive FGR pregnancies, SVR, AIx and UtA mean PI were significantly higher (p 0.01 for all), while CO was not significantly different (p = 0.429). Conclusion FGR is associated with maternal cardiovascular changes. The conflicting results reported by previous studies could be explained by failure to correct for maternal body surface area, incorrectly labelling SGA pregnancies as FGR, or lack of distinction between FGR with or without maternal hypertension.

O112. Inotropy index and ratio of potential to kinetic energy: Two novel parameters derived from continuous-wave Doppler ultrasound

Objective In pregnancies complicated by hypertension, antihypertensive therapy should be tailored to the type of hypertension, whether cardiogenic or vasogenic. However, current clinical assessment does not allow this differentiation. Inotropy is a measure of the myocardial contractility, while the ratio of potential to kinetic energy (PKR) is a measure of arterial impedance. In a recent report, both Smith-Madigan inotropy index (SMII) and PKR could be derived from a continuous-wave Doppler ultrasound technique. The aim of this study was to investigate these two novel cardiovascular parameters in pregnancies complicated by hypertensive disorders compared to uncomplicated pregnancies. Methods This was a prospective case-control study including a group of women presenting with hypertension in the second half of the pregnancy and a group of uncomplicated pregnancies recruited after 20 weeks' gestation. Cardiovascular parameters were assessed using a continuous-wave Doppler ultrasound technique (USCOM®). Pregnancies were followed up and the outcome ascertained. Mann–Whitney test and regression analysis were used for statistical analysis. Results We recruited 94 women with hypertensive disorders in pregnancy and 106 controls. Compared to normotensive controls, the cases had significantly higher SMII (median 1.96W/m 2 , IQR 1.64–2.40 vs 1.75W/m 2 , IQR 1.47–2.03, p p 5 /m 2 , IQR 2170–3023 vs 1877dynes-sec/cm 5 /m 2 , IQR 1561–2233, p 2 , IQR 2.97–4.0 vs 3.72L/min/m 2 , IQR 3.17–4.40, p =0.003). Conclusion Women presenting with hypertensive disorders in pregnancy demonstrate significant changes in cardiac contractility and dynamic arterial impedance. It remains to be established whether these indices may be used prospectively for the individualized triage and management of these pregnancies.

Complications of Pregnancy in Women with Thrombotic Thrombocytopenic Purpura

AbstractAbstract 3322 BackgroundThrombotic Thrombocytopenic Purpura (TTP) occurring in association with pregnancy or puerperium accounts for 12–25% of all TTP acute episodes. Pregnancy leads to acute TTP in women affected by congenital TTP in the absence of periodic prophylactic plasma infusions, while the risk of acute TTP during pregnancy for women with the acquired form is not well known. Moreover, it is not known whether the presence of anti-ADAMTS13 antibodies that characterize acquired TTP affect the outcome of subsequent pregnancies. The aim of this study was to evaluate maternal-foetal outcome of pregnancies started after the diagnosis of TTP. MethodsWe analyzed clinical and laboratory features of 25 pregnancies of 22 women with TTP (all acquired TTP) out of 320 TTP patients in our cohort, all referred to the Milan TTP Registry, Milan (Italy), from 1994 to 2012. We tested the available biological samples for ADAMTS13 activity using FRET method, anti-ADAMTS13 autoantibodies by Western Blotting and ultra-large von Willebrand Factor (ULVWF) multimers ratio. ResultsWe found that 18 out of 25 pregnancies (72%) were complicated by either TTP recurrence (11/25, 44%) or spontaneous abortion in the first trimester (7/25, 28%). The incidence of TTP recurrence was 0.02 cases/week gestation (median duration of pregnancy at event: 32 weeks). The incidence of spontaneous abortion was 0.01 cases/week gestation (median duration of pregnancy at event: 6 weeks). Women’s parity was associated with spontaneous abortion, with a relative rate of 2.8 (95% confidence interval: 0.5–14.2) for multigravidae versus primigravidae.Interestingly, almost all miscarriages (6/7, 86%) occurred in women who experienced a pregnancy-related TTP episode during a previous pregnancy. To understand if this high rate of spontaneous abortion could be related to TTP, we analyzed ADAMTS13 activity levels, anti-ADAMTS13 antibodies and ULVWF multimers pattern. In the pregnancies complicated by TTP relapse, ADAMTS13 activity was severely reduced in the acute phase, in association with the presence of antiADAMTS13 antibodies and reduction of ULVWF multimers (ULVWF ratio < 0.85); in the cases of pregnancies complicated by spontaneous abortion, the mean ADAMTS13 activity level in the first trimester was 31%, with the presence of antiADAMTS13 antibodies and excess of ULVWF multimers (ULVWF ratio > 1.21); in the group of uncomplicated pregnancies, the mean ADAMTS13 activity levels was 97% in the first trimester and remained > 35% until delivery, with absence of antiADAMTS13 antibodies and normal ULVWF multimers. ConclusionsObstetric complications are frequent during pregnancies in women affected with acquired TTP. ADAMTS13 activity levels > 35% in the absence of antiADAMTS13 antibodies seem to confer little or no risk, while lower ADAMTS13 activity levels and the presence of antiADAMTS13 antibodies during pregnancy are predictive of poor gravidic outcome, either with acute TTP or spontaneous abortion in the first trimester. Surprisingly, although confidence intervals were wide, miscarriage rates were highest in multigravidae. Pre-gravidic and gravidic monitoring of ADAMTS13 activity levels and anti-ADAMTS13 autoantibodies is crucial in the management of pregnancies in TTP patients. Disclosures:No relevant conflicts of interest to declare.

An increase of elastic tissue fibers in blood vessel walls of placental stem villi and differences in the thickness of blood vessel walls in third trimester pre-eclampsia pregnancies

Abstract This study has goals of examining whether pre-eclampsia may lead to an increase of elastic tissue fibers in blood vessel walls of placental stem villi or whether there are differences in the thickness of blood vessel walls within these villi when compared to normotensive pregnant women. Non-infarcted placental tissue samples from 28 participants with uncomplicated pregnancies and 26 patients with pre-eclampsia were obtained. After routine histological procedures, the sections were processed either for conventional Verhoeff staining for the demonstration of elastic fiber system. Paraffine sections from placenta biopsies prepared for light microscopic examination were gathered. In uncomplicated pregnancies, terminal villi blood vessels were observed with no stained elastic tissue fibers in most areas. In the pre-eclampsia pregnancy of human placenta, the elastic fibers significiantly increased in terminal villi blood vessel walls which were dark in color, using Verhoeff’s tissue stain, when comparing with the uncomplicated pregnancy group. Our results indicate that an increase of elastic tissue fibers in blood vessels of placental stem villus and terminal villi, and also an increase of wall thickness during pre-eclampsia.

Newborns of pre‐eclamptic women: a biochemical difference present in utero

Offspring exposed to pre-eclampsia in utero had higher systolic blood pressure, and were more obese during adolescence. We hypothesized that metabolic changes, a marker of cardiovascular disease, may be affected by intrauterine exposure to pre-eclampsia. Blood samples were collected from cord blood of 36 newborns who were exposed to pre-eclampsia in utero and their mothers, and of 35 newborns and their mothers with noncomplicated pregnancies. Serum levels of lipids, homocysteine, and fibrinogen were determined in all samples. Fetuses exposed to pre-eclampsia in utero had lower birth weight, smaller abdominal circumference (p<0.002; p<0.03 respectively) and higher levels of low-density lipoprotein, homocysteine, and fibrinogen (p<0.01; p<0.001; p<0.001, respectively), compared with fetuses of normotensive, pregnancies. A significant correlation existed between maternal homocysteine concentration and that of newborn infants (r=0.539; p<0.001) and between maternal low-density lipoprotein and newborn homocysteine (r=0.36; p<0.03). Significant negative correlations were found between abdominal circumference of newborns and cord blood concentration of fibrinogen (r= - 0.52; p<0.001) and low-density lipoprotein (r= - 0.42; p<0.001). Maternal plasma homocysteine, low-density lipoprotein, and triglyceride were significantly higher, while high-density lipoprotein was significantly lower in pregnancies with pre-eclampsia as compared with the uncomplicated pregnancy group (p<0.001 for all). Cord blood level of low-density lipoprotein and fibrinogen were best predicted by abdominal circumference of newborn, though maternal level of homocysteine was the most powerful independent predictor of cord homocysteine. Intrauterine exposure to pre-eclampsia was associated with untoward effects on biochemical risk factor markers for cardiovascular disease. Our findings suggest that the cardiovascular risk of newborns of pre-eclamptic mothers may begin in utero.

Fetal Growth Retardation And Its Relationship To Maternal Blood Lead Levels, Antioxidants And Pregnancy Induced Hypertension

Lead intoxication in human being has been documented since the second century BC and its deleterious effects continue to be a major health hazard for the population, it is demonstrated that lead exposure might decrease the defense mechanism of the cell to the oxidative stress, and therefore, elevate the reactive oxygen species (ROS) generation which enhance vascular reactivity. Since vitamin E (Vit. E) and vitamin C (Vit. C) are natural antioxidants, changes in their status may reflect alterations in free radical production rate and their concentrations are biological markers of oxidative stress. This study was conducted to determine the relationship between maternal blood lead levels and the antioxidants Vit.E and Vit.C in a step to understand the mechanism of action of lead and its possible influence on maternal blood pressure and fetal growth at the lower community exposure levels. The study included, 42 patients with pregnancy induced hypertension (PIH) with or without proteinuria, 31 patients with fetal growth retardation (FGR) and 23 women with uncomplicated pregnancy. We demonstrated that, the maternal blood lead levels were significantly high in the PIH (30.5 ±0.978 μg/dl) and FGR groups (28.87 ±1.21 μg/dl) as compared with the uncomplicated pregnancy group (17.82 ±110μg/dl) at P≤0.00l Vit.E concentrations were significantly lower in both PIH and FGR (0.941 ±0.033 mg/dl and 0.866 ± 0.055 mg/dl respectively) when compared with normal group (2.00±0.085 mg/dl). Regarding Vit.C in the 2 studied groups there was significantly low levels in PIH group (0.772 ±0.030 mg/dl and FGR (0.847 ±0.039 mg/dl) in comparison with control group (l.23 ±0.06 mg/dl). We observed significant negative correlation between maternal blood lead levels and Vit.E in PIH and FGR group. A significant negative correlation was also observed between maternal lead levels and Vit.C in both studied groups. We concluded that high blood lead levels in pregnancy are associated with low Vit.E , Vit.C, FGR and PIH. Such association or relationship could not be causal and more longitudinal studies are needed to confirm the link between lead, lipid peroxidation, antioxidants and pregnancy complications. This study may help in raising our consciousness of our environment and the need to protect us. The lack of effective and safe treatments for low-level intoxication has to promote environmental intervention to control different sources of lead to reduce lead burden among women and their newborns and to protect the fetus from other intrauterine toxic exposure that might be injurious.

Fetal Growth Retardation And Its Relationship To Maternal Blood Lead Levels, Antioxidants And Pregnancy Induced Hypertension

Lead intoxication in human being has been documented since the second century BC and its deleterious effects continue to be a major health hazard for the population, it is demonstrated that lead exposure might decrease the defense mechanism of the cell to the oxidative stress, and therefore, elevate the reactive oxygen species (ROS) generation which enhance vascular reactivity. Since vitamin E (Vit. E) and vitamin C (Vit. C) are natural antioxidants, changes in their status may reflect alterations in free radical production rate and their concentrations are biological markers of oxidative stress. This study was conducted to determine the relationship between maternal blood lead levels and the antioxidants Vit.E and Vit.C in a step to understand the mechanism of action of lead and its possible influence on maternal blood pressure and fetal growth at the lower community exposure levels. The study included, 42 patients with pregnancy induced hypertension (PIH) with or without proteinuria, 31 patients with fetal growth retardation (FGR) and 23 women with uncomplicated pregnancy. We demonstrated that, the maternal blood lead levels were significantly high in the PIH (30.5 ±0.978 μg/dl) and FGR groups (28.87 ±1.21 μg/dl) as compared with the uncomplicated pregnancy group (17.82 ±110μg/dl) at P≤0.00l Vit.E concentrations were significantly lower in both PIH and FGR (0.941 ±0.033 mg/dl and 0.866 ± 0.055 mg/dl respectively) when compared with normal group (2.00±0.085 mg/dl). Regarding Vit.C in the 2 studied groups there was significantly low levels in PIH group (0.772 ±0.030 mg/dl and FGR (0.847 ±0.039 mg/dl) in comparison with control group (l.23 ±0.06 mg/dl). We observed significant negative correlation between maternal blood lead levels and Vit.E in PIH and FGR group. A significant negative correlation was also observed between maternal lead levels and Vit.C in both studied groups. We concluded that high blood lead levels in pregnancy are associated with low Vit.E , Vit.C, FGR and PIH. Such association or relationship could not be causal and more longitudinal studies are needed to confirm the link between lead, lipid peroxidation, antioxidants and pregnancy complications. This study may help in raising our consciousness of our environment and the need to protect us. The lack of effective and safe treatments for low-level intoxication has to promote environmental intervention to control different sources of lead to reduce lead burden among women and their newborns and to protect the fetus from other intrauterine toxic exposure that might be injurious.

Placental ratio in pregnancies at different risk for intrauterine growth

Objective: We have analyzed the placental/birthweight ratio in women at increased risk of intrauterine growth retardation and pregnancy-induced hypertension and in women with pregnancy `complicated' by these conditions. Study design: A total of 89 women with small gestational age (SGA) infants, 355 with appropriate gestational age infants (200 in the uncomplicated pregnancy group) and 28 with large for gestational age (LGA) infants were considered. Results and Conclusion: The mean placental weight showed a significant increase from the SGA to the LGA in the two groups. The placental ratio tended to increase from the LGA group to the SGA one both in infants of women with uncomplicated pregnancy and with pregnancy complicated by intrauterine growth retardation or pregnancy-induced hypertension; these findings were statistically significant.

Plasma interleukin-1α, interleukin-1β and interleukin-1 receptor antagonist levels in pre-eclampsia

The values of plasma interleukin-1α (IL-1α), interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1ra) levels were evaluated as the markers of pre-eclampsia in 35 serial plasma samples from ten pregnant women who subsequently developed pre-eclampsia and in 74 plasma samples from 20 uncomplicated pregnancies, retrospectively. No correlation was found between plasma IL-1α, IL-1β and IL-1ra levels, liver and renal function tests. thrombocyte and white blood cell counts, proteinuria, systolic and diastolic blood pressures and gestational weeks. Almost equal levels of IL-1α and IL-1β were measured in all corresponding groups, but these were too few in number to statistically analyze. IL-1ra values were higher in the pre-eclampsia group than in the uncomplicated pregnancy group, at 20–25 and 31–35 gestational weeks significantly and 26–30 gestational weeks insignificantly and showed an increase during labor in both groups. It was found to have 58% positive predictivity, 100% negative predictivity, 50% specificity and 100% sensitivity at gestational weeks 20–25. According to these results, IL-1ra seems to be considered for its high negative predictivity in the exclusion of the probability of pre-eclampsia development during antenatal visits, but its plasma level is not correlated with the severity of the disease.

Doppler ultrasonography of the umbilical cord in complicated pregnancies.

Ninety-two gravid women had Doppler insonation of the umbilical cord after diagnosis of various pregnancy complications. Calculations of the systolic-diastolic (S/D) ratio were plotted against a nomogram of values developed at the Hospital of the University of Pennsylvania. An S/D ratio greater than the 95th percentile for gestational age correctly predicted 58% of women who became preeclamptic and 61% of infants who were small for gestational age (SGA). Of those fetuses with an elevated S/D ratio, 42% suffered fetal distress as defined by an abnormal fetal heart rate tracing, a 1- or 5-minute Apgar score less than 5 or 7, respectively, or a cord blood pH determination less than 7.20; 60% required operative delivery; and 49% stayed in the hospital longer than 5 days or were admitted to the Neonatal Intensive Care Unit (NICU). All these values are significantly greater than those obtained in a control group of uncomplicated pregnancies or a group of women with similar pregnancies, but with normal measurements of the umbilical artery S/D ratio. Moreover, 69% of abnormally elevated umbilical artery S/D ratios were detected at or before 30 weeks' gestation. Calculation of an S/D ratio of the umbilical cord greater than the 95th percentile for gestational age is an early and sensitive predictor of poor perinatal outcome.