Maternal Circulating Placental Growth Factor and Neonatal Metabolic Health Biomarkers in Small for Gestational Age Infants (original) (raw)
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Diabetologia, 2021
Aims/hypothesis Maternal hyperglycaemia alone does not explain the incidence of large offspring amongst women with type 1 diabetes. The objective of the study was to determine if there is an association between placental function, as measured by angiogenic factors, and offspring birthweight z score in women with type 1 diabetes. Methods This cohort study included samples from 157 Continuous Glucose Monitoring in Pregnant Women with Type 1 Diabetes (CONCEPTT) trial participants. Correlations were estimated between birthweight z score and placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) levels measured at baseline and at 24 and 34 weeks of gestation. Linear regression was used to assess the relationship between birthweight z score and placental health, as measured by PlGF and sFlt-1/PlGF ratio, stratified by glycaemic status (continuous glucose monitoring and HbA 1c measures) and adjusted for potential confounders of maternal BMI, smoking and weight gain. Higher PlGF levels and lower sFlt-1/PlGF ratios represent healthy placentas, while lower PlGF levels and higher sFlt-1/PlGF ratios represent unhealthy placentas. Results Among CONCEPTT participants, the slopes relating PlGF levels to birthweight z scores differed according to maternal glycaemia at 34 weeks of gestation (p = 0.003). With optimal maternal glycaemia (HbA 1c < 48 mmol/mol [6.5%]/ or continuous glucose monitoring time above range ≤ 30%), birthweight z scores were reduced towards zero (normal weight) with increasing PlGF values (representing a healthy placenta), and increased with decreasing PlGF values. With suboptimal glycaemic status (HbA 1c ≥ 48 mmol/mol [6.5%] or time above range > 30%), increasing PlGF values were associated with heavier infants. Those with a healthy placenta (PlGF > 100) and suboptimal glycaemic control had a higher mean z score (2.45) than those with an unhealthy placenta (mean z score = 1.86). Similar relationships were seen when using sFlt-1/PlGF ratio as a marker for a healthy vs unhealthy placenta. Conclusions/interpretation In women with type 1 diabetes, infant birthweight is influenced by both glycaemic status and placental function. In women with suboptimal glycaemia, infant birthweight was heavier when placentas were healthy. Suboptimal placental function should be considered in the setting of suboptimal glycaemia and apparently 'normal' birthweight.
BJOG: An International Journal of Obstetrics and Gynaecology, 1998
Objective To determine whether there is a relationship between maternal serum insulin-like growth factor-I and fetal growth, consistent with the hypothesis that insulin-like growth factor-I influences maternal constraint upon fetal growth by controlling placental transfer. Design A prospective, observational study. Setting Fetal medicine unit and antenatal clinic of a large teaching hospital. Population One hundred and forty-one pregnant women identified as having small or normally grown fetuses. Methods Fetuses were scanned every two weeks with maternal venesection at each visit. Cases (birthweight < 5th centile) were assigned to two groups: fetal growth restriction due to placental dysfunction (umbilical artery Doppler, growth velocity pulsatility index > +2 SD; n = 25) and normal small-for-gestational-age (normal Doppler, growth velocity and amniotic fluid; n = 27). Eighty-nine controls had birthweights between the 5th and the 95th centiles, normal Doppler, growth velocity and amniotic fluid. Insulin-like growth factor-I was measured by radioimmunoassay, and its relationship to gestational age and birthweight was assessed by regression analysis. Comparisons between case groups were made by Student's t test or analysis of covariance to allow for the effect of birthweight. Outcome measure The last insulin-like growth factor-I level before delivery within the different subgroups. Results In controls, maternal insulin-like growth factor-I increased with gestational age (r = 0.40; P = 0.0001) but did not correlate with birthweight. Insulin-like growth factor-I was low in the mothers of growth restricted fetuses (-1.56 SD; P = O.OOOl), but not in those with small-forgestational age fetuses. Conclusions The control and small-for-gestational-age data suggest that maternal insulin-like growth factor-I is not associated with endocrine control of normal placental function. Low insulin-like growth factor-I relates to poor placental transfer, as indicated by Doppler, rather than to low birthweight. Whether this is a regulatory mechanism, a cause or a consequence of placental dysfunction needs further study.
Archives of Medical Research, 2006
Background. Low birthweight has been associated with an increased risk of obesity, insulin resistance, and diabetes in adulthood. The aim of this study was to evaluate IGF-I, adiponectin, insulin levels, and body fat in small-for-gestational-age (SGA) infants at birth. Methods. We performed a transverse comparative study in SGA and appropriate-forgestational-age (AGA) infants. The study was conducted at the Hospital of Gynecology and Obstetrics in Leon, Mexico. Weight, length, and percent of body fat were evaluated during the first 48 h of birth. Glucose, insulin, leptin, adiponectin, and IGF-I levels in cord blood were measured. Results. We studied 100 infants (50 SGA and 50 AGA). A history of diabetes in a second-degree relative was higher in SGA infants than in AGA infants (48.0 vs. 30.0%, respectively; p 5 0.03). Glucose, adiponectin, insulin and IGF-I levels were similar between the groups. Leptin levels and percentage of body fat were lower in SGA than AGA (15.3 vs. 23.4 ng/mL; p 5 0.003, 11.1 vs. 12.7%; p !0.001, respectively). Logistic regression analysis showed that length, percentage of body fat, and leptin levels were positively associated with birthweight. However, leptin levels were not independent of percentage of body fat. Conclusions. Low body fat and leptin levels, but no evidence of increased metabolic risk at birth, were found in SGA infants.
Metabolism, 2014
Objective. To examine maternal serum concentrations of placental growth factor (PlGF) at 11-14 gestational weeks in pregnancies that developed gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Methods. Case control study including 40 GDM cases and 94 controls. PlGF, biophysical and biochemical markers and maternal-pregnancy characteristics were analyzed. Results. Log 10 transformed PlGF (log 10 PlGF) was not related to maternal factors. Log 10 PlGF was increased (p = 0.008) in the GDM group compared to the control group. Log 10 PlGF was associated with fasting glucose levels (p = 0.04) in the oral glucose tolerance test. Log 10 PlGF had a strong relation with birth weight adjusted for gestational age in the control but not in the GDM group.
Hormone Research in Paediatrics, 2007
Background: The maternal insulin-like growth factor (IGF) system is considered to be involved in fetal growth regulation. However, available data linking this system to fetal growth are contradictory and incomplete. Aims: To measure components of the IGF system before, during and after pregnancy in healthy women and to relate these results, and their changes during pregnancy, to fetal weight (gestational week 31) and birth weight. Methods: Serum concentrations of IGF-I, IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3 and IGFBP-3 protease activity were assessed in 23 women before conception, at weeks 8, 14, 20, 32 and 35 of pregnancy and 2 weeks postpartum. The data were analyzed using simple and multiple linear regression. Results: One third of the variability in fetal weight was explained by IGF-I in combination with IGFBP-3 protease activity, both assessed at gestational week 32 (p = 0.013). Birth weight was negatively correlated (r = –0.43 to –0.59) with IGFBP-1 at gestational wee...
Maternal insulin-like growth factor binding protein-1, body mass index, and fetal growth
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2000
Aim-To examine the hypothesis that the maternal insulin-like growth factor system may constrain fetal growth. Methods-A prospective observational study of maternal serum insulin-like growth factor binding protein-1 (IGFBP-1) and fetal growth was undertaken in neonates with birthweights below the 5th centile. They had been classified either as having fetal growth restriction (FGR) due to placental dysfunction (increased umbilical artery Doppler pulsatility index (PI); n = 25) or as being small for gestational age (SGA; normal umbilical artery PI, growth velocity and amniotic fluid; n = 27). Eighty nine controls had normal birthweights (5th-95th centile), umbilical artery PI, growth velocity, and amniotic fluid. IGFBP-1 was measured by radioimmunoassay. Results-Among the controls, there was no significant correlation between IGFBP-1 and birthweight after allowing for body mass index (BMI). Maternal BMI was high in FGR and after adjusting for this, IGFBP-1 was increased (109 ng/ml) compared with SGA babies (69 ng/ml) and controls (57 ng/ml) and correlated with the umbilical artery PI. Conclusions-Maternal IGFBP-1 is probably not part of normal placental function. Its increase in FGR could be the cause or consequence of impaired placental perfusion, but high IGFBP-1 concentrations might further reduce the availability of maternal IGF-I to the placenta. This could worsen placental function and so adversely aVect fetal growth.
Hormones (Athens, Greece)
Childhood obesity and the Metabolic Syndrome (MetS) are associated with an increased risk for early onset endothelial dysfunction and atherosclerosis. Placental growth factor (PlGF), a member of the vascular endothelial growth factor family, plays an important role in atherosclerosis by stimulating angiogenesis and atherogenic migration of monocytes/macrophages into the arterial wall. The aim of this study was to investigate differences in circulating PlGF concentrations between children with obesity/metabolic syndrome and non-obese children. We have previously shown increased high-sensitivity troponin (hs-TnT) concentrations in children with MetS from the same cohort. Fifty-seven obese (49 without and 8 with MetS) and 25 non-obese children (controls) were assessed at the Childhood Obesity Clinic of our Department. Obesity was defined using the IOTF criteria. MetS was defined based on the IDF criteria. PlGF was measured using electrochemiluminescence methodology. Mean PIGF concentra...
Journal of Pediatric Endocrinology and Metabolism, 2001
This study was planned to investigate the relationship between birth weight and insulinlike growth factor-I (IGF-I),IGF binding protein-3 (IGFBP-3), and leptin levels in neonates with normal growth (appropriate for gestational age: AGA) and retarded growth (small for gestational age: SGA); and to evaluate these growth factors’ effects in early postnatal growth. All newborns were full-term: gestational age 38-41 weeks. Of 50 neonates, 25 were SGA. IGF-I, IGFBP-3 and leptin levels were measured in maternal serum and venous cord blood at birth and at 15 days of life of neonates using specific RIAs. Maternal serum leptin concentrations were significantly higher than cord blood leptin concentrations (p <0.001). Maternal serum IGF-I, IGFBP-3 and leptin levels did not show correlations with birth weight. In contrast, there were significantly positive correlations between birth weight and venous cord blood IGF- I, IGFBP-3 and leptin levels (p <0.001). In the SGA group, the newborns wi...
Maternal body mass index and placental weight: a role for fetal insulin, maternal insulin and leptin
Journal of Endocrinological Investigation
Purpose Placental weight (PW) has been found to mediate the main effect of maternal BMI on fetal size. Still, the BMI–PW association is poorly understood. Therefore, we aimed to explore potential explanatory variables, including gestational weight gain (GWG), early- and late-pregnancy circulating levels of maternal glucose, insulin, leptin, adiponectin, triglycerides, LDL-C, and HDL-C, and fetal insulin. Methods We included two studies of pregnant women from Oslo University Hospital, Norway: the prospective STORK (n = 263) and the cross-sectional 4-vessel method study (4-vessel; n = 165). We used multiple linear regression for data analyses. A non-linear BMI-PW association was observed, which leveled off from BMI25. Therefore, BMI <25 and ≥25 were analyzed separately (n = 170/122 and 93/43 for STORK/4-vessel). Confounding variables included maternal age, parity, and gestational age. Results PW increased significantly per kg m−2 only among BMI <25 (univariate model’s std.β[p] =...