Development Of Macrosomia Research Articles

Binge alcohol drinking before pregnancy is closely associated with the development of macrosomia: Korean pregnancy registry cohort.

Alcohol drinking during pregnancy has been well-known to cause the detrimental effects on fetal development; however, the adverse effects of pre-pregnancy drinking are largely unknown. We investigate whether alcohol drinking status before pregnancy is associated with the risk for macrosomia, an offspring's adverse outcome, in a Korean pregnancy registry cohort (n = 4,542) enrolled between 2013 and 2017. Binge drinking was defined as consuming ≥5 drinks on one occasion and ≥2 times a week, and a total 2,886 pregnant, included in the final statistical analysis, were divided into 3 groups: never, non-binge, and binge drinking. The prevalence of macrosomia was higher in binge drinking before pregnancy than those with never or non-binge drinking (7.5% vs. 3.2% or 2.9%, p = 0.002). Multivariable logistic regression analysis demonstrated an independent association between macrosomia and prepregnancy binge drinking after adjusting for other confounders (adjusted odds ratio = 2.29; 95% CI, 1.08-4.86; p = 0.031). The model added binge drinking before pregnancy led to improvement of 10.6% (95% CI, 2.03-19.07; p = 0.0006) in discrimination from traditional risk prediction models. Together, binge drinking before pregnancy might be an independent risk factor for developing macrosomia. Intensified intervention for drinking alcohol in women who are planning a pregnancy is important and may help prevent macrosomia.

IGF2-derived miR-483-3p contributes to macrosomia through regulating trophoblast proliferation by targeting RB1CC1

What is the role of insulin-like growth factor 2 (IGF2)-derived miR-483-3p in macrosomia? IGF2-derived intronic miR-483-3p is overexpressed in macrosomia placentas, and miR-483-3p prompts HTR-8/SVneo extravillous trophoblast cell line proliferation through down-regulation of its target RB1 inducible coiled-coil 1 (RB1CC1). Macrosomia is a common pregnancy-associated disease and causes a number of adverse maternal and perinatal outcomes. The development of macrosomia is reportedly attributable to over proliferation of the placental cells. MicroRNAs (miRNAs) play an important role in the development of fetal and placenta by regulating their target genes. Here, we investigated the role of IGF2-derived intronic miR-483-3p in macrosomia. The expression of IGF2, miR-483-3p and its target gene in placental tissues from 30 pregnant women who had macrosomia was compared to those of 30 gestation-matched healthy pregnant controls. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR-8/SVneo cell was used. Placenta tissues were collected from pregnant women who had macrosomia without diabetes or other complications (n = 30) and healthy pregnant controls (n = 30). HTR-8/SVneo cells were transfected with specific miRNA mimics or inhibitors. MiRNA and mRNA isolated from placenta tissues or cells were measured by quantitative real-time PCR. Protein was measured by western blot. Cell proliferation was assayed using a colorimetric proliferation assay method. Cell cycle and apoptosis were analyzed by flow cytometry. The putative targets of miR-483-3p were predicted using the TargetScan, miRanda, miRDB and DIANA algorithms. Dual luciferase reporter assay was used to measure the relationship of miR-483-3p and RB1CC1. IGF2-derived miR-483-3p was overexpressed in macrosomia placentas. miR-483-3p promoted proliferation in HTR-8/SVneo cells and had a positive relationship with its host gene IGF2. Subsequently, RB1CC1 was confirmed as a direct target of miR-483-3p, which may be an important mediator of cell growth regulation for miR-483-3p. N/A. The level of IGF2 and its intronic miR-483-3p in the serum of these participants was not investigated. Further studies are required to understand the mechanisms underlying the cause of the increase of IGF2 and miR-483-3p in macrosomia. These findings give a new insight into the role of intronic miRNA and its host gene in the development of macrosomia. Furthermore, it may offer a new target for prognostic and therapeutic intervention for macrosomia. This work was supported by awards from National Natural Science Foundation of China (Nos. 81401213, 81673217, 81703260), Jiangsu Provincial Medical Youth Talent (No. QNRC2016110), Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents, the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine), the Education Department of Jiangsu Province (No. 16KJB330010), the Science and Technology Department of Jiangsu Province (No. BK20160227), the China Postdoctoral Science Foundation funded project (No. 2016M601892). The authors declare no competing financial interests.

The World Health Organization fetal growth charts: concept, findings, interpretation, and application.

Ultrasound biometry is an important clinical tool for the identification, monitoring, and management of fetal growth restriction and development of macrosomia. This is even truer in populations in which perinatal morbidity and mortality rates are high, which is a reason that much effort is put onto making the technique available everywhere, including low-income societies. Until recently, however, commonly used reference ranges were based on single populations largely from industrialized countries. Thus, the World Health Organization prioritized the establishment of fetal growth charts for international use. New fetal growth charts for common fetal measurements and estimated fetal weight were based on a longitudinal study of 1387 low-risk pregnant women from 10 countries (Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) that provided 8203 sets of ultrasound measurements. The participants were characterized by median age 28 years, 58% nulliparous, normal body mass index, with no socioeconomic or nutritional constraints (median caloric intake, 1840 calories/day), and had the ability to attend the ultrasound sessions, thus essentially representing urban populations. Median gestational age at birth was 39 weeks, and birthweight was 3300 g, both with significant differences among countries. Quantile regression was used to establish the fetal growth charts, which also made it possible to demonstrate a number of features of fetal growth that previously were not well appreciated or unknown: (1) There was an asymmetric distribution of estimated fetal weight in the population. During early second trimester, the distribution was wider among fetuses <50th percentile compared with those above. The pattern was reversed in the third trimester, with a notably wider variation >50th percentile. (2) Although fetal sex, maternal factors (height, weight, age, and parity), and country had significant influence on fetal weight (1-4.5% each), their effect was graded across the percentiles. For example, the positive effect of maternal height on fetal weight was strongest on the lowest percentiles and smallest on the highest percentiles for estimated fetal weight. (3) When adjustment was made for maternal covariates, there was still a significant effect of country as covariate that indicated that ethnic, cultural, and geographic variation play a role. (4) Variation between populations was not restricted to fetal size because there were also differences in growth trajectories. (5) The wide physiologic ranges, as illustrated by the 5th-95th percentile for estimated fetal weight being 2205-3538 g at 37 weeks gestation, signify that human fetal growth under optimized maternal conditions is not uniform. Rather, it has a remarkable variation that largely is unexplained by commonly known factors. We suggest this variation could be part of our common biologic strategy that makes human evolution extremely successful. The World Health Organization fetal growth charts are intended to be used internationally based on low-risk pregnancies from populations in Africa, Asia, Europe, and South America. We consider it prudent to test and monitor whether the growth charts' performance meets the local needs, because refinements are possible by a change in cut-offs or customization for fetal sex, maternal factors, and populations. In the same line, the study finding of variations emphasizes the need for carefully adjusted growth charts that reflect optimal local growth when public health issues are addressed.

Influence of pre-pregnancy obesity on the development of macrosomia and large for gestational age in women with or without gestational diabetes mellitus in Chinese population

To determine the effects of gestational diabetes mellitus (GDM) and pre-pregnancy obesity on macrosomia and large for gestational age (LGA). We conducted a prospective cohort study of 587 GDM women and 478 non-GDM women from 2012 to 2013. We collected their data of the pre-pregnancy weight, sociodemographic data, medical histories, clinical treatment, and followed-up the outcomes of delivery including birth weight. Multiple logistic regression models were used to test associations between pre-pregnant obesity and macrosomia/LGA and between GDM and macrosomia/LGA. Of 1065 women we studied, obese women had 4.17 times and 2.27 times increased risk of developing macrosomia (95% CI: 2.52 to 6.91) and LGA (95% CI: 1.60 to 3.21), respectively, than non-obese women after adjustment for maternal age, gestational weeks and GDM. We did not find GDM is a risk factor for macrosomia or LGA after GDM treatment. Pre-pregnancy obesity accounts for a high prevalence of macrosomia. Interventions that focus on pre-pregnancy obesity have the potential to reach far more women at risk of macrosomia.

Role of metformin pregravid preparation patients with prediabetes impaired glucose toletance

Tasks of investigation were concluded the characterization of insulin resistence (IR) and hormonal features in patients with prediabetes and influence of diet or metformin on the course of pregnancy and perinatal complications. There were examined 61 womans. The OGTT, definition of insulin levels in plasma and index IR were performed in all patiens. OGTT and index IR were normal in 14 womans (control group I). OGTT was normal but index IR was impared in 33 womans (group IR - II). From this group 22 womans were treated with diet (II A group) and 11 womans treated with metformin (IIB group). OGTT and index IR were abnormal in 14 womans (impared OGTT - III group), they were treated with metformin. Dose of metformin was 1500 mg/d, threatment was continueted for 3-4 manths. Conclusion: Used indexes IR basal and two hour after glucose load were significant in definition of normal and decreased insulin sensitivity (IR). Presence of IR is accompanied by high level of free testosterone in blood without impared secretion of ovarian and suprarenal androgens. There was impared sensitivity of endometrium of secretory stage. The frequency of obstetric and perinatal complications in patients receiving diet not differ from patients treated with metformin. There was only a tendercy to low frequency of threatening miscarriages befor 12 weeks of gestations in paitiens receiving metformin. Development of GDM was observed in 13,1 % of patiens only with presence of IR. The use of metformin in pregravidal stage preserved the development of macrosomia in offsprings of patients with prediabetes.

Aberrant upregulation of miR-21 in placental tissues of macrosomia

With China's rapid economic growth in the past 3 decades, an increase in rate of macrosomia has been reported in China. Fetal growth is a result of multiple factors including genetic potential for growth, maternal nutrition, maternal metabolism, endocrine factors and placental perfusion and function. However, the detailed mechanism of how macrosomia happened remains poorly known. Recent studies showed that the expression of a number of microRNAs (miRNAs) in placentas is involved in fetal growth. We hypothesized that aberrant expression of microRNA-21 (miR-21) and microRNA-16 (miR-16) in placenta is associated with macrosomia. Using quantitative real time PCR, we analyzed the expression level of miR-21 and miR-16 in terminal placentas of macrosomia pregnancies (n=35) and normal controls (n=35). Potential target genes of miRNA were predicted using TargetScan, miRanda and PicTar. Target genes were mapped to KEGG pathways using KEGG Mapper with an in-house Perl script with KEGG Gene IDs. MiR-21 showed significant up-regulation in macrosomia (P=0.037). After controlling the potential confounders, multivariable logistic regression analysis suggested the risk of macrosomia increased, multivariable adjusted ORs of macrosomia for those in the highest tertile was 3.931 (95%CI: 1.049-14.736) compared with those in the lowest tertile in terms of miR-21 level. The target genes of miR-21 were involved in eight possible signaling pathways. They were pathways in P53 signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, TGF-beta signaling pathway and PI3K-Akt signaling pathway (P<0.001), Wnt signaling pathway, Jak-STAT signaling pathway and mTOR signaling pathway (P<0.05). Our study is the first to investigate the association between placental miRNA expression and macrosomia. Our results indicate that the expression level of miR-21 in placental tissue may be involved in the development of macrosomia.

Macrosomia prediction using different maternal and fetal parameters in women with 50 g glucose challenge test between 130 and 140 mg/dl

Our aim in this study was to investigate the association between 1-h glucose challenge test (GCT) of 130-140 mg/dl and the development of macrosomia. In this retrospective cohort study, patients with GCT between 130 and 140 mg/dl were divided into two groups. Macrosomic and appropriate-for-gestational-age (AGA) term neonates were compared for the presence of maternal risk factors and fetal abdominal circumference between 29 and 34 weeks. There were no significant differences between the groups with respect to maternal age, parity, BMI at the first trimester and at the time of GCT, gestational weeks at delivery. However; history of a macrosomic baby delivery was significantly higher in macrosomic group (33.3% for group 1, 11.3% for group 2, p = 0.001). Abdominal circumference at 29-34 weeks of gestations was significantly higher in macrosomic group (32.46 ± 1.97 for group 1 vs. 31.06 ± 2.46 for group 2, p = 0.002). History of a macrosomic baby delivery and abdominal measurement at 29-34 weeks was important predictors of macrosomia in patients with GCT between 130 and 140 mg/dl.

Levels of insulin-like growth factors and their receptors in placenta in relation to macrosomia.

To investigate the associations between mRNA levels that encodes for insulin-like growth factors (IGFS) and their receptors in term placenta, and the risk of macrosomia. Term placentas were collected from 37 neonates with macrosomia and 37 neonates with normal birth weight in Changzhou Women and Children Health Hospital from March 1 to June 30, 2008. The IGF mRNA levels and their receptors in those placentas were measured by Real-time PCR. The placental weight was positively correlated with the birth weight both in the macrosomia group (r=0.550, p=0.004) and the control group (r=0.678, p=0.000). After adjusting for potential confounders, multivariable adjusted ORs of neonates with macrosomia for those in the increasing two tertiles were 17.3 (95%CI: 2.50-19.2) and 5.94 (95%CI: 0.96, 36.8), respectively, compared with those in the lowest tertile in terms of IGF-IImRNA level. Similarly, multivariable adjusted ORs of neonates with macrosomia for those in the increasing two tertiles of IGF-IR mRNA were 25.3 (95%CI: 3.43-187) and 43.0 (95%CI: 4.89, 378), respectively. These results indicate that the levels of placental IGF-IIand IGF-IR mRNA may be involved in the development of macrosomia.

Evaluation of the BSI-18 for measurement of psychological distress in pregnant women

IN PREGNANT WOMEN ASAD SHEIKH, RHONDA JOHNSON, MADHURI MULEKAR, CHERYL CRICHLEY, PATRICIA SCOTT, University of South Alabama, Obstetrics and Gynecology, Mobile, Alabama, University of Oklahoma, Department of Obstetrics and Gynecology, Oklahoma City, Oklahoma, University of South Alabama, Mobile, Alabama OBJECTIVE: Psychological distress (PS) is the emotional experience of an individual that may interfere with their ability to cope. It may not be evident to the health care provider until the patient reaches an observable crisis event. Obstetric care providers are frequently faced with management dilemmas of pregnant patients with possible psychological distress. Clinicians could greatly benefit from a rapid, simple, accurate and inexpensive screening tool to identify those patients in distress and to monitor therapy. The Brief Symptom Index – 18 (BSI-18) has been developed as a rapid (four minutes to complete) tool to screen for distress in cancer and psychiatric patients. We hypothesized that the distress scores on the BSI-18 and Brief Symptom Index (BSI) will be highly comparable in pregnant women also. STUDY DESIGN: 78 pregnant women attending the high risk clinic at the University of Oklahoma were enrolled. They were given the BSI test. A subset of 18 questions composing the BSI-18 was also separately analyzed. The degree of psychological distress was reported as the Global Severity Index (GSI). Data were analyzed by paired t-test, Chi-square, ANOVA, Pearson’s correlation coefficient and regression analysis. Differences were considered significant when P!0.05. RESULTS: The BSI-18 is an abbreviated form of the BSI and evaluates three symptom scales (depression, anxiety and somatization) and one global index (GSI). In contrast, the BSI measures nine symptom scales and three global indexes. The correlation between the BSI and BSI-18 was extremely strong (r = 0.98). Similarly, the scores for the anxiety and somatization subscales as well as the GSI were highly correlated between the two test forms (r = 0.95, r = 0.87 and r = 0.89 respectively). CONCLUSION: The results support the use of the BSI-18 in pregnancy as a psychological screening tool for distress. 283 LOWER BIRTHWEIGHTS IN GRAVID AFRICAN AMERICANS WITH DIABETES KALEE AHLIN, JENNIFER AHN, LAURA DIGIOVANNI, University of Chicago, OB/GYN, Chicago, Illinois OBJECTIVE: Maternal diabetes and maternal obesity are important risk factors for the development of fetal macrosomia. In contrast, certain racial ethnicities, particularly African Americans, are at increased risk for low birthweight infants. Our objective was to determine if African American ethnicity is a protective factor against macrosomia in pregnancies complicated with diabetes. STUDY DESIGN: We performed a retrospective chart review of all pregnancies complicated with diabetes at the University of Chicago from January 1, 1999-December 31, 2004. Inclusion criteria were: 1) singleton pregnancy, 2) gestational age 36 weeks at delivery, and 3) Diabetic White classification A-R. Subjects were classified by maternal ethnicity as Caucasian, African American, Hispanic, Asian or Other. A total of 767 patients met inclusion criteria for the study. We compared the differences in prevalence of macrosomia or birthweight across each ethnic group using univariant or multivariant analysis. RESULTS: Development of macrosomia (O4000 gm) between the different ethnic groups was not statistically significant (p=0.74). Univariate analysis also found similar birthweights in each ethnic group (p=0.21). However, in a multivariante regression analysis using baby weight, with race, age, Body Mass Index (BMI), hypertension and glycosylated hemoglobin as covariants, our African American patients had significantly lower birthweights compared with the referenced Caucasian group (3352 gm and 3395 gm, respectively, p=0.03). Our African American patients had a larger than average BMI (38.5GSD 9.04 kg/m) compared with other ethnic groups (BMI 33.1 GSD 6.48 kg/m) (p!0.001). CONCLUSION: There was no statistical difference in the development of macrosomia among each ethnic group. However, despite having significantly higher BMIs, the African American patients with pregnancies complicated by diabetes had smaller birthweight infants. This study suggests that ethnicity may be a protective factor against larger infants in gravid African American patients with diabetes.

Diabetes in pregnancy: fetal macrosomia, hyperinsulinism, and islet hyperplasia in the offspring of rats subjected to temporary protein-energy malnutrition early in life.

The effect of temporary, severe protein-energy malnutrition in young female rats on the fetal and maternal outcome of subsequent pregnancy has been investigated. Female rats were fed a low-protein diet between 3 and 6 wk of age. During this period, growth was stunted, glucose tolerance impaired, and insulin secretory response to glucose almost absent. Upon refeeding normal diet, growth was resumed and glucose tolerance normalized, but a subnormal insulin secretory response to glucose and a reduced pancreatic B-cell mass persisted into adult life. During pregnancy, such rats had a glucose tolerance with wide excursions of the serum glucose concentrations and an exaggerated insulin secretory response compared with normal rats. The previously malnourished rats also expanded their B-cell mass during pregnancy to the level of normal rats. The incidence of fetal loss and malformations was not increased in the offspring of previously malnourished rats. At term, the viable offspring were heavier than those of normal rats and had an increased pancreatic insulin content and an increased pancreatic B-cell mass. It is concluded that temporary protein-energy malnutrition in young rats reduces the ability to increase insulin production to meet the needs of pregnancy. The capacity for glucose disposal is decreased and glucose and other nutrients are transferred to the fetus in increased amounts. This stimulates pancreatic B-cell growth and the development of macrosomia in the offspring, well recognized features of diabetic pregnancy. The long-term consequences of malnutrition are thus not restricted to the malnourished but may also be inflicted on subsequent generations.

Pregnancy outcome in insulin-dependent diabetes: temporal relationships with metabolic control during specific pregnancy periods.

There are specific temporal relationships between metabolic control during different periods of pregnancy and outcome in insulin-dependent diabetic pregnancies. The rate of spontaneous abortions correlates with poor periconceptional glycemic control. Major malformations and decreased infant bone mineral content at birth correlate with poor first trimester glycemic control. Increased rates of preeclampsia and premature labor correlate with poor glycemic control in the second trimester. The development of macrosomia and that of neonatal hypoglycemia correlate with poor third trimester glycemic control. Perinatal asphyxia and neonatal hypoglycemia correlate with hyperglycemia in labor. We suggest that each stage of the pregnancy, if complicated by poor glycemic control, may lead to specific, temporally related complications. Glycemic control from the periconceptional period to the time of delivery appears important in order to minimize complications of the insulin-dependent diabetic pregnancy.