Correlation of placental pathology and perinatal outcomes with Hemoglobin A1c in early pregnancy in gravidas with pregestational diabetes mellitus

IntroductionData on the correlation among Hemoglobin A1c (HbA1c), placental pathology, and perinatal outcome in the pregestational diabetic population is severely lacking. We believe that this knowledge will enhance the management of pregnancies complicated by pregestational diabetes. We hypothesize that placental pathology correlates with glycemic control at an early gestational age.MethodsThis is a retrospective cohort study conducted from 2003 to 2011 at a large tertiary care center. Women included had a singleton gestation, preexisting diabetes mellitus, and information about delivery and placental pathology available for review. Placental pathology and perinatal outcomes were compared across three groups of patients with differing HbA1c levels (<6.5%, 6.5–8.4%, and ≥8.5%).Results293 placentas were examined. HbA1c was measured at a mean of 9.5week gestation. Median HbA1c was 7.5%, interquartile range 6.5%–8.9%. 23% of the cohort had HbA1c <6.5%, 41.9% between 6.5% and 8.4%, and 34.8% > 8.5%. BMI varied significantly by group (35.4 vs. 34.4 vs. 32.0 respectively, P = 0.04). Individual placental lesions did not vary with HbA1c levels. The incidence of acute chorioamnionitis differed significantly in the type 1 population and “distal villous hypoplasia” varied in the type 2 population.DiscussionThe results show that HbA1c values in early pregnancy are poor predictors of future placental pathologies. As a result, HbA1c values obtained during early gestation (which reflect the level of glycemic control over an extended period of time) do not correlate with any particular placental pathology, despite reflecting the potential for placental insults secondary to pre-gestational diabetes.     

Pregnancy planning in women with pregestational diabetes

Objectives.?Women with pregestational diabetes are advised to plan their pregnancies to optimize glycemia and reduce fetal complications. We evaluated the adequacy of pregnancy planning effort and medical planning in pregnant women with type 1 and type 2 diabetes.

Methods.?This retrospective cohort study surveyed pregnant women with pregestational diabetes mellitus between 2006 and 2008 in Ontario, Canada. We evaluated three measures of pregnancy planning: pregnancy planning effort, medical planning based on prepregnancy glycemic control, and folic acid use. We compared women with type 1 and type 2 diabetes and explored predictors of pregnancy planning.

Results.?Of the 163 women studied (89 type 1, 74 type 2 diabetes), 47% reported high pregnancy planning effort, 58% reported attempts to optimize glycemic control, and 56% took folic acid before pregnancy. Of those who reported high pregnancy planning, 20% did not medically plan their pregnancies. Rates were similar between women with type 1 and type 2 diabetes. The most important predictor of pregnancy planning was having discussed plans with their physician.

Conclusions.?Our findings suggest that pregnancy planning is suboptimal in women with both type 1 and type 2 diabetes, highlighting a need to improve preconception counseling for all women with pregestational diabetes.     

Obstetric outcomes and placental findings in gestational diabetes patients according to maternal prepregnancy weight and weight gain

Objective: We assessed clinical outcomes and placental pathology among pregnancies complicated with gestational diabetes mellitus (GDM) according to their pregestational body mass index (BMI) and weight gain during pregnancy.

Study design: Pregnancy outcome and placental pathological reports of all GDM deliveries, during 2009–2015, were reviewed. We compared women with pregestational BMI?>?30 and or gestational weight gain >20?kg (high-BMI group), and women with pregestational BMI?Results: Out of the 429 women with GDM, 221 (51.5%) were in the high-BMI group and 208 (48.3%) were in the normal BMI group. As compared to the normal BMI group, the high-BMI group displayed a higher rate of GDMA2 41.6 versus 30.2%, p?=?.01, higher birth weight, 3475?±?508?g versus 3242?±?503?g, p?p?p?=?.07, respectively. By logistic regression analysis, past CD and high BMI were independently associated with CD, while GDM type and birth weight were nonsignificant. Pathological reports were available for 143 of these patients. Placental weight was increased among the high-BMI group, but did not retain significance after adjustment for birth weight, and GDM type. No differences were demonstrated in other placental histological findings.

Conclusions: GDM pregnancies accompanied by increased weight gain or elevated pregestational BMI are associated with adverse obstetric outcomes, despite similar placental findings. Patient should be advised accordingly, as gestational weight gain may determine delivery mode.     

Mitochondrial content and hepcidin are increased in obese pregnant mothers

Objective: Maternal obesity is characterized by systemic low-grade inflammation and oxidative stress (OxS) with the contribution of fetal sex dimorphism. We recently described increased mitochondrial content (mtDNA) in placentas of obese pregnancies. Here, we quantify mtDNA and hepcidin as indexes of OxS and systemic inflammation in the obese maternal circulation.

Methods: Forty-one pregnant women were enrolled at elective cesarean section: 16 were normal weight (NW) and 25 were obese (OB). Obese women were further classified according to the presence/absence of maternal gestational diabetes mellitus (GDM); [OB/GDM(–)]: n?=?15, [OB/GDM(+)]: n?=?10. mtDNA and hepcidin were evaluated in blood (real-time PCR) and plasma (ELISA).

Results: mtDNA and hepcidin levels were significantly increased in OB/GDM(–) versus NW, significantly correlating with pregestational BMI. Male/female (M/F) ratio was equal in study groups, and overall F-carrying pregnancies showed significantly higher mtDNA and hepcidin levels than M-carrying pregnancies both in obese and normal weight mothers.

Conclusions: Our results indicate a potential compensatory mechanism to increased obesity-related OxS and inflammation, indicated by the higher hepcidin levels found in obese mothers. Increased placental mitochondrial biogenesis, due to lipotoxic environment, may account for the greater mtDNA amount released in maternal circulation. This increase is namely related to F-carrying pregnancies, suggesting a gender-specific placental response.     

Diabetes gestacional: su complejidad y repercusión en la evolución del embarazo y salud del recién nacido

ObjectiveTo establish distinct risk groups for the development of perinatal complications in women with gestational diabetes.Patients and methodsWe studied 115 women with gestational diabetes managed in our center from January 2001 to January 2004. For statistical analysis the SPSS 11.0 package was used.ResultsWomen with earlier onset of gestational diabetes required higher doses of insulin therapy and at an earlier gestational age than women with later onset. A higher body mass index at the beginning of pregnancy was also associated with the need for higher insulin doses to control diabetes.ConclusionWomen with onset of gestational diabetes early in pregnancy and high pregestational body mass index should be considered as a group at high risk and should be closely followed-up with more active treatment and suitable ultrasonographic monitoring.     

The risk of preeclampsia beyond the first pregnancy among women with type 1 diabetes parity and preeclampsia in type 1 diabetes

AimTo estimate the incidence of preeclampsia (PE) among nulliparous and multiparous patients with type 1 diabetes and to study predictors of PE.MethodsWe prospectively collected data on all pregnancies of patients with pregestational type 1 diabetes, followed at our Prenatal Medicine Unit between 1993 and 2008. Medical records were prospectively reviewed by two obstetricians for maternal demographics, pregnancy data, maternal and fetal outcomes. Data were analyzed according to the development of PE and parity.ResultsWe identified and collected data on 291 eligible pregnancies (195 among nulliparae and 96 among multiparae). The incidence of PE was 9.2% (95% CI: 5.6–14.2) among nulliparae and 9.4% (95% CI: 4.4–17.0) among multiparae. Patients who developed PE had higher HbA1c during pregnancy compared to patients who did not (p = 0.026 among nulliparae and p = 0.032 among multiparae). Chronic hypertension [OR 17.12 (3.22, 91.00)], microalbuminuria at the beginning of the pregnancy [OR 3.77 (1.22, 11.61)], weight gain during pregnancy [OR 1.13 (1.04, 1.23)] and HbA1c in the first trimester [2.81 (1.12, 7.05)], but not parity, were significant predictors of PE.ConclusionsAmong patients with type 1 diabetes the incidence of PE was similar among nulliparae and multiparae, unlikely in the general population where PE is a disease of the first pregnancy. An increased risk of PE should be assumed for both nulliparous and multiparous women with pregestational diabetes.     

The prevalence of congenital malformations is still higher in pregnant women with pregestational diabetes despite near-normal HbA1c: a literature review

Aims/hypothesis: We assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational (type 1 or type 2) diabetes and investigated if the rate of congenital malformations was similar in women with near-normal glycemic control compared to the background population. We also assessed the association between congenital malformations and maternal hyperglycemia in pregnant women with pregestational diabetes with special focus on women with near-normal HbA1c in early pregnancy.

Materials and methods: This is a literature review based on an electronic literature search of the databases PubMed, Cochrane, Embase and Web of Science conducted in July 2017 using the search terms diabetes, pregnancy, HbA1c or glycemic control and congenital anomaly or congenital anomaly. We included original papers in English published after 1997 with data on congenital malformations and HbA1c in at least 250 women with pregestational diabetes.

Results: Nine papers with in total 6225 women with type 1 diabetes and 2334 women with type 2 diabetes were included. The prevalence of congenital malformations was 6.4% in women with type 1 diabetes and 4.3% in women with type 2 diabetes and for the combined group of women with pregestational diabetes, the relative risk compared to the background population was 3.2. In women with HbA1c?Conclusions: In pregnant women with pregestational diabetes the prevalence of congenital abnormalities was threefold higher in women with pregestational diabetes compared to the background population. However, HbA1c below 53?mmol/mol (7.0%) in early pregnancy was also associated with a two times increased risk of congenital malformations compared to the background population.     

Placental maternal vascular malperfusion and adverse pregnancy outcomes in gestational diabetes mellitus

IntroductionMaternal vascular malperfusion (MVM) lesions represent hypoxic-ischemic damage to the placenta, and they are associated with adverse pregnancy outcomes. Women with gestational diabetes (GDM) are at increased risk for pregnancy complications, so we set out to characterize the prevalence and clinical correlates of MVM lesions in this cohort.MethodsThis was a retrospective cohort study of 1187/1374 (86.4%) women with GDM delivered between 2009 and 2012 who had placental pathology available. Placental lesions of all types were tabulated and grouped into constructs of related entities. MVM lesions specifically included villous infarcts, decidual vasculopathy, increased syncytial knots, perivillous fibrin, and fibrin deposition. We compared maternal characteristics between women with and without MVM lesions, and we also assessed the impact of these lesions on birth weight, preterm birth, and pre-eclampsia using multivariable logistic regression analysis.ResultsMVM lesions were the most common placental lesion type in women with GDM (n = 362, 30.5%). Excess gestational weight gain was independently associated with MVM lesions (aOR 1.42, 95% CI 1.06–1.91, p = 0.02) after adjusting for maternal characteristics. MVM lesions were associated with lower birth weight (−90.3 g, 95% CI -148.0 to −32.7, p = 0.002), as well as a 2-fold increased risk for delivery of a small for gestational age infant (10.8 vs 5.9%, p = 0.01) in overweight and obese women. MVM lesions were also associated with increased risk for preterm birth <34 weeks (adjusted OR 2.36, 95% CI 1.31–4.23, p = 0.004) and hypertensive disorders of pregnancy (HDP; adjusted OR 1.58, 95% CI 1.13–2.22, p = 0.02).DiscussionPlacental maternal vascular malperfusion lesions may be one pathway linking excess gestational weight gain to adverse pregnancy outcomes in women with GDM, and future studies are needed to identify metabolic factors that may explain this association.     

No change in calreticulin with fetal growth restriction in human and rat pregnancies

Introduction

Calreticulin is a ubiquitously expressed protein that was detected in the circulation and is significantly increased in maternal blood during human pregnancy compared to the non-pregnant state. Calreticulin is further increased in the plasma of women with the pregnancy-related disorder pre-eclampsia compared to normotensive pregnancy. The aims of this study were to compare calreticulin in human pregnancy with calreticulin in rat pregnancy, and to compare calreticulin during fetal growth restriction with normal control pregnancies.

Methods

Women were recruited who either had normal pregnancies or had pregnancies complicated with fetal growth restriction; maternal blood samples and placentas were collected. Blood was also taken from women who were not-pregnant. Growth restriction was induced in pregnant rats by uterine vessel ligation; blood and placental samples were collected. Blood was also taken from non-pregnant rats. Western blot was used to quantify the placental expression of calreticulin and the concentrations of calreticulin in plasma.

Results

Although calreticulin was significantly increased in maternal plasma during human pregnancy compared to the non-pregnant state; it did not increase in plasma during rat pregnancy. These results suggest that there may be differences in the role of extracellular calreticulin in human compared to rat pregnancy. Calreticulin was not significantly altered in either placental extracts or maternal plasma in both the human and rat pregnancies complicated by fetal growth restriction compared to gestational matched control pregnancies.

Conclusion

This study found that there was no change in calreticulin during human pregnancy complicated with fetal growth restriction or when growth restriction is induced in rats.     

Analysis of correlations between the placental expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus

Purpose: The aim of the study was to analyze the correlations between the expression of glucose transporters GLUT-1, GLUT-4, and GLUT-9 in human term placenta and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus (DM).

Materials and methods: Placental samples were obtained from healthy control (n?=?25) and diabetic pregnancies, including diet-controlled gestational diabetes mellitus (GDMG1) (n?=?16), insulin-controlled gestational diabetes mellitus (GDMG2) (n?=?6), and pregestational DM (PGDM) (n?=?6). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected glucose transporter proteins. For the purposes of correlation analysis, the following parameters were selected: type of diabetes, gestational age, maternal prepregnancy body mass index (BMI), gestational weight gain, third trimester glycated hemoglobin concentration, placental weight, fetal birth weight (FBW) as well as ultrasonographic indicators of fetal adiposity, including subscapular (SSFM), abdominal (AFM), and midthigh (MTFM) fat mass measurements.

Results: In the PGDM group, the analysis demonstrated positive correlations between the placental expression of GLUT-1, GLUT-4, and GLUT-9 and FBW, AFM, and SSFM measurements (p?p?p?p?Conclusions: The study results revealed that placental expression of GLUT-1, GLUT-4, and GLUT-9 may be involved in the intensification of the fetal growth in pregnancies complicated by GDM/PGDM.     

A comparison of lispro and regular insulin for the management of type 1 and type 2 diabetes in pregnancy.

OBJECTIVE: To describe perinatal outcomes of women with pregestational diabetes treated with short-acting, regular insulin and the short-acting insulin analogue, lispro. STUDY DESIGN: This was a prospective observational study of women with pregestational diabetes maintained on short-acting insulin regimens over a 3-year period. Clinical characteristics, aspects of diabetic therapy, and perinatal/neonatal outcomes were collected. RESULTS: Of 107 women, 49 were maintained on regular insulin and 58 utilized the insulin analogue, lispro. Frequency of type 1 diabetes, maternal age, overweight/obese pregravid body mass index (> or =25 kg/m2), preexisting hypertension, and presence of vascular disease were similar between groups. Women treated with lispro had a longer duration of diabetes (11.4 vs. 8.3 years, p = 0.04). Glycemic control was improved in women managed with lispro compared to regular insulin (HgbA1c 5.9 vs. 6.7, p = 0.009). Total insulin requirements were lower in the lispro group in the first (0.58 vs. 0.79 units/kg, p = 0.02), second (0.75 vs. 1.10 units/kg, p = 0.002), and third (0.98 vs. 1.25 units/kg, p = 0.03) trimesters of pregnancy. Mean infant birth weight was greater in the lispro group, whereas the rate of large for gestational age infants and ponderal indices were similar between groups. Malformation rate, gestational age at delivery, neonatal intensive care unit admission, neonatal length of stay, rates of respiratory distress syndrome, and hypoglycemia were similar. CONCLUSIONS: Women treated with lispro demonstrated improved glycemic control and lower total insulin requirements during pregnancy compared to those receiving regular insulin. Perinatal outcomes were similar between women treated with both types of insulin.     

Breastfeeding predicts the risk of childhood obesity in a multi-ethnic cohort of women with diabetes

Objective.?To determine whether breastfeeding reduced the risk of childhood obesity in the infants of a multi-ethnic cohort of women with pregestational diabetes.

Methods.?In this retrospective cohort study, women with pregestational diabetes were mailed a questionnaire about breastfeeding and current height and weight of mothers and infants. Predictors of obesity (weight for age >85 percentile) were assessed among offspring of index pregnancies, using univariate and multivariable logistic regression.

Results.?Of 125 women, 81 (65%) had type 1 diabetes and 44 (35%) had type 2 diabetes. The mean age of offspring was 4.5 years. On univariate analysis, significant predictors of obesity in offspring were type 2 diabetes (odds ratio, OR 2.4, 95% confidence interval, CI 0.99–5.72); maternal body mass index (BMI)?>?25 (OR 4.4, 95% CI 1.4–19.4); and any breastfeeding (OR 0.22, 95% CI 0.07–0.72). After multivariable adjustment, breastfeeding (OR 0.20, 95% CI 0.06–0.69) and having an overweight/obese mother (OR 3.49, 95% CI 1.03–16.2) remained independently associated with childhood obesity.

Conclusion.?Breastfeeding significantly decreased the likelihood of obesity in offspring of mothers with pregestational diabetes, independent of maternal BMI and diabetes type. Women with diabetes should be encouraged to breastfeed, given the increased risk of obesity in their children.     

Effects of Women’s Weight Changes on Adverse Outcomes in a Second Pregnancy

ObjectiveTo estimate the effects of women’s weight changes in four sequential perinatal periods across first and second pregnancies (pregravid, first gestation, interpregnancy, second gestation) on adverse maternal and neonatal outcomes in the second pregnancy while accounting for interdependencies in weight across the four periods (Aim 1) and to test the influence of the sequential path of weight changes through the four perinatal periods of risk on maternal and neonatal outcomes in the second pregnancy (Aim 2).DesignSecondary data analysis.SettingThirty-one Wisconsin hospitals.SampleWomen with 24,795 linked records from first and second births from 2006 through 2013.MethodsWe used a fully recursive system of linear and logistic regression equations to examine the relationships among weight changes in the four perinatal periods with maternal (gestational diabetes mellitus, gestational hypertension, cesarean birth) and neonatal (macrosomia, small for gestational age, large for gestational age, low birth weight, congenital anomalies, and perinatal death) adverse outcomes in the second pregnancy.ResultsPregravid weight was weakly and inconsistently associated with weight changes in subsequent periods. Each 5-kg incremental weight change in the first pregnancy, interpregnancy, and second pregnancy contributed to a 0.75- to 5-kg weight change in subsequent periods, 9% to 25% change in risk for adverse maternal outcomes, and 8% to 47% change in risk for adverse neonatal outcomes in the second pregnancy. Fluctuations in weight across pregnancies and associations with outcomes were strongest among normal-weight and overweight women.ConclusionWeight changes across two pregnancies affected maternal and neonatal outcomes in the second pregnancy in all body mass index categories; the larger weight fluctuations observed in normal and overweight women were associated with greater risk of adverse outcomes. Attention to pregnancy weight during and between pregnancies is important for targeted weight counseling to reduce risks in subsequent pregnancies.     

Association of first-trimester angiogenic factors with placental histological findings in late-onset preeclampsia

ObjectiveTo explore in women with late-onset preeclampsia (PE) the association between maternal levels of angiogenic/antiangiogenic factors in the first trimester of pregnancy and histological findings attributable to placental underperfusion (PUP).MethodsA nested case-control cohort study was conducted in 73 women with pregnancies complicated by late-onset PE (>34 weeks at delivery) matched with controls. First trimester uterine artery Doppler (UtA); maternal levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were retrieved. Placentas were histologically evaluated using a hierarchical and standardized classification system. One-way ANOVA with linear polynomial contrast or linear-by-linear association test was performed to test the hypothesis of a linear association across study groups (controls, PE without PUP and PE with PUP).ResultsIn 54 (74%) placentas, 89 placental histological findings qualifying for PUP were found. Across study groups, significant values were observed in maternal levels of decreased PlGF (MoM values: 1.53, 1.41 and 1.37; p < 0.001), increased sFlt-1 (MoM values: 3.11, 3.11 and 3.22; p = 0.002), increased sFlt-1/PlGF ratio (MoM values: 2.3, 2.3 and 2.44; p < 0.001), abnormal UtA Doppler (MoM values: 1, 1.26 and 1.32; p < 0.001), and worse perinatal outcomes in terms of gestational age at delivery, cesarean section for not reassuring fetal status, birth weight and neonatal acidosis.DiscussionIn late-onset PE an imbalance of circulating angiogenic and anti-angiogenic factors already present at 8–10 weeks of pregnancy was associated with histological findings reflecting placental insufficiency. An early first trimester screening by angiogenic factors might help to identify patients with placental involvement among late-onset PE cases.ConclusionIn late-onset preeclampsia, first-trimester uterine Doppler and circulating levels of angiogenic/antiangiogenic factors are associated with placental underperfusion.     

Perinatal outcomes in pregnancies complicated by type 1 diabetes mellitus

Abstract

The aim of this study was to explore the risk of perinatal outcomes in pre-gestational type 1 diabetes mellitus (T1DM) compared to gestational diabetes mellitus (GDM) and pregnancy without diabetes and to examine the association of glycemic level of third-trimester gestation with perinatal outcomes in T1DM. We included 69 pre-gestational T1DM, 1398 cases of GDM, and 1304 control pregnancies and collected data regarding demographics, obstetric, and perinatal outcomes from the hospital discharge database. Relative to the pregnancies without diabetes, women with T1DM encountered increasing risk of polyhydramnios, preterm delivery, and cesarean section. These adverse outcomes were also common in GDM, although with relatively lower adjusted ORs. The weights of babies delivered by women with T1DM were more intend to be large for gestational age, as well as to be less than 2.5?kg relative to those without diabetes. Poorly controlled hemoglobin A1c in late pregnancy was significantly associated with an increased risk of preterm birth in T1DM (adjusted odds ratio 2.01, 95%confidence interval 1.1–3.6). Women with T1DM have considerably increased risks of adverse perinatal outcomes, which appear more prevalent than the perinatal outcomes in women with GDM. Thus, a specific routine is required for pregnancy in T1DM to improve the glycemic control and obstetric care.     

Placental abnormalities associated with isolated single umbilical artery in small-for-gestational-age births

BackgroundPrevious studies have shown that pregnancies complicated by placentas with an isolated single umbilical artery (iSUA) are at increased risk for small-for-gestational-age (SGA) births. The etiology of SGA in this population, however, remains unknown.ObjectiveThe primary objective of this study was to evaluate whether placental abnormalities in pregnancies with SGA births differ according to the presence of iSUA.Study designThis was an observational study of all women with pathologic examination of the placenta after delivering a non-anomalous, singleton SGA neonate between January 2009 and August 2015. SGA was defined as birthweight less than 10th percentile for gestational age. Women were categorized according to whether they had an iSUA or a three-vessel cord. The following placental pathologies were compared between the groups using bivariable and multivariable analyses: SGA placenta, maternal vascular malperfusion, high grade fetal vascular malperfusion, and chronic villitis.Results1833 women were included in the analysis: 34 with iSUA and 1799 with three-vessel cord. More than 85% of women in both groups had at least one placental abnormality. After adjusting for nulliparity and neonatal gender, the presence of iSUA was associated with increased odds of high grade fetal vascular malperfusion (adjusted odds ratio 2.8, 95% confidence interval 1.1–7.5) and decreased odds of maternal vascular malperfusion (adjusted odds ratio 0.2, 95% confidence interval 0.1–0.9). There was no significant association with other pathologic findings.ConclusionPathologic placental findings associated with SGA birth differed based on umbilical cord composition. The presence of iSUA in an SGA birth was associated with a higher odds of high grade fetal vascular malperfusion abnormalities and lower odds of maternal vascular malperfusion abnormalities, compared to SGA birth with a 3VC.     

Adolescent Pregnancy Outcomes in the Province of Ontario: A Cohort Study

ObjectiveFew Canadian studies have examined the association between adolescent pregnancy and adverse pregnancy outcomes The objective of this cohort study was to characterize the association between adolescent pregnancy and specific adverse maternal, obstetrical, and neonatal outcomes, as well as maternal health behaviours.MethodsWe conducted a retrospective population-based cohort study of all singleton births in Ontario between January 2006 and December 2010, using the Better Outcomes Registry & Network database Outcomes for pregnant women < 20 years of age (adolescent) were compared with those of women 20 to 35 years old (adult).ResultsThis study included 551 079 singleton birth records, 23 992 (4.35%) of which derived from adolescent pregnancies. Adolescents had a higher rate of smoking and substance use than adult women and were within the lowest education and family income quintiles. Adolescents had a significantly lower risk of gestational hypertension (adjusted relative risk [aRR] 0.73) and gestational diabetes (aRR 0.34), placental abruption (aRR 0.80), and placenta previa (aRR 0.36), but their risk of preterm premature rupture of membranes was significantly higher (RR 1.16). Adolescents had a significantly higher proportion of spontaneous vaginal delivery (aRR 1.76), significantly lower rates of use of epidural analgesia (aRR 0.93), of Caesarean section (aRR 0.57), and of assisted vaginal delivery (aRR 0.76), but a significantly higher risk of emergency CS (aRR 1.31). Neonates with an adolescent mother had significantly higher risks of admission to NICU (aRR 1.08) and very preterm birth (aRR 1.16). There was no significant difference between the two groups in rates of small for gestational age babies, low birth weight, preterm birth, and fetal death. Adolescents had significantly lower rates of prenatal class attendance, prenatal visits in the first trimester, and breastfeeding.ConclusionThis large Canadian cohort study confirms that, compared with adults, adolescents have improved outcomes such as lower rates of gestational hypertension, gestational diabetes, antepartum hemorrhage, and operative deliveries However, adolescents also have higher sociodemographic risk factors and seek prenatal care later than adults These risk factors in combination with young age, lead to other important maternal, obstetrical, and neonatal adverse outcomes. These findings highlight the importance of multidisciplinary prenatal management in the adolescent population to address their high-risk needs, to ensure healthy pregnancies, and to reduce adverse perinatal outcomes.     

Maternal vascular malperfusion of the placental bed associated with hypertensive disorders in the Boston Birth Cohort

IntroductionThe associations of maternal conditions, before or during pregnancy, with placental lesions have not been adequately studied in populations.MethodsIn the Boston Birth Cohort, we evaluated associations between three maternal medical conditions (hypertensive disorders [HDs], gestational/pre-gestational diabetes and obesity), and placental histological findings, using a standardized classification system proposed by the Amsterdam Placental Workshop Group. Placental pathology diagnoses and clinical data from 3074 mothers with clinical indications who delivered singleton live births at the Boston Medical Center between October 1998 and November 2013 were evaluated. Associations between each maternal condition and maternal vascular malperfusion (MVM) of the placental bed and its standardized subgroups were examined using multivariate logistic and multinomial regressions.ResultsWomen with HDs (chronic hypertension, eclampsia, preeclampsia, HELLP syndrome) had significantly increased odds of MVM lesions when compared to women with no HD (aOR 2.08 95% CI 1.74–2.50), after adjusting for demographics, substance use, diabetes and body mass index. No significant differences in frequencies or aORs were seen in women with and without diabetes, or across body mass index categories. Co-morbid condition patterns that included HDs were more likely to be associated with MVM than those without.DiscussionUsing a standardized classification system, we showed that MVM is strongly and specifically associated with maternal HDs, but not other maternal conditions. Additional studies are needed to confirm and validate our findings, and evaluate the role of maternal vascular lesions of the placental bed in relation to postnatal growth and development of the offspring and effect modifiers.     

Negative regulators of Wnt signaling pathway SFRP1 and SFRP3 expression in preterm and term pathologic placentas

Objective: Since Wnt signaling pathway plays a pivotal role in the placental development, we explored the expression of its negative regulators, SFRP1 and SFRP3 proteins in placentas from pathological pregnancies and compared their levels with those in healthy placentas.

Methods: Placentas (n?=?79) were stained for SFRP1, and SFRP3 proteins by immunohistochemistry and their expression levels were quantified by stereological variable of volume density (Vv, mm°).

Results: Significantly higher expressions of SFRP1 and SFRP3 were found in all investigated groups of term and preterm pathologic placentas as well as in preterm control placentas in comparison with normal-term placentas.

Conclusions: Our findings indicate the active involvement of negative Wnt regulators SFRP1/SFRP3 in placental development and important role in pathology of pregnancy.     

Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia.

OBJECTIVE: To compare placental pathology between women with and without thrombophilia who had severe preeclampsia, intrauterine growth retardation, severe abruptio placentae, or stillbirth. METHODS: After delivery, 68 women with singleton pregnancies with one of the above complications were evaluated for an inherited thrombophilia: factor V Leiden, methylenetetrahydrofolate reductase and prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin III. Thirty-two women were thrombophilic (group A), and 36 women were not (group B). There was no difference in maternal age, parity, and type of pregnancy complication. A single pathologist examined each placenta. RESULTS: The gestational age at delivery, birth weight, and placental weight were significantly lower in group A. Three parameters showed significant differences between the groups: thrombophilic women had a higher number of villous infarcts (P <.01), more multiple infarcts (P <.05), and a higher incidence of placentas with fibrinoid necrosis of decidual vessels (P <.05). CONCLUSION: Placentas of women with severe complications and thrombophilia have an increased rate of vascular lesions.