The value of fetal growth biometry velocities to predict large for gestational age (LGA) infants

Author(s):  
Jared T. Roeckner ◽  
Linda Odibo ◽  
Anthony O. Odibo
2020 ◽  
Vol 26 (8) ◽  
pp. 624-635
Author(s):  
C Roeca ◽  
E Silva ◽  
C Barentsen ◽  
T L Powell ◽  
T Jansson

Abstract In studies of human IVF, as compared to frozen embryo transfer (ET), fresh ET is associated with smaller infants and higher risk of small for gestational age infants. Recent observations suggest that ET using vitrified embryos is associated with higher pregnancy and live birth rates compared to fresh ET, but increased rates of large for gestational age infants. The mechanisms underlying these associations are largely unknown, and available evidence suggests that the influence of IVF, vitrification and the superovulated (SO) uterine environment on placental function and fetal growth is complex. This warrants further investigation given the prevalent practice in human IVF of both fresh ET into a SO uterine environment, and vitrification with ET into a more physiologic uterine environment. Using a mouse model that closely resembles human IVF, we investigated if vitrification of IVF embryos better preserves placental function and results in better pregnancy outcomes as compared to fresh ET because of transfer into a more physiologic endometrium. We found that the SO environment, independent of vitrification status, reduced implantation rates, inhibited placental mechanistic target of rapamycin signaling and induced placental stress signaling, resulting in fetal growth restriction (1.080 ± 0.05 g estrous fresh (n = 17 litters), 1.176 ± 0.05 g estrous vitrified (n = 12), 0.771 ± 0.06 g SO fresh (n = 15), 0.895 ± 0.08 g SO vitrified (n = 10), P < 0.0001). In addition, our study suggests that vitrification impairs the developmental potential of IVF blastocysts that resulted in a significantly smaller litter size (2.6 ± 2.3 fresh estrous vs 2.5 ± 2.4 fresh SO vs 1.6 ± 1.7 estrous vitrified vs 1.7 ± 1.8 SO vitrified, P = 0.019), with no effect on fetal growth or placental function at term. Our findings suggest that vitrification may negatively impact early embryonic viability, while the SO maternal uterine environment impairs both placental development and fetal growth in IVF.


2021 ◽  
Vol 8 ◽  
Author(s):  
Tai-Ho Hung ◽  
Chung-Pu Wu ◽  
Szu-Fu Chen

Background: Dysregulation of placental mechanistic target of rapamycin (mTOR) activity has been implicated in the pathophysiology of pregnancies complicated by idiopathic fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) with large-for-gestational-age (LGA) infants. However, the underlying mechanisms remain unclear.Methods: We obtained placentas from women with normal pregnancies (n = 11) and pregnancies complicated by FGR (n = 12) or GDM with LGA infants (n = 12) to compare the levels of total and phosphorylated forms of Akt, AMPK, TSC2, and mTOR among the three groups and used primary cytotrophoblast cells isolated from 30 normal term placentas to study the effects of oxygen–glucose deprivation (OGD) and increasing glucose concentrations on the changes of these factors in vitro.Results: Placentas from FGR pregnancies had lower phosphorylated Akt (p-Akt) levels (P < 0.05), higher p-AMPKα levels (P < 0.01), and lower mTOR phosphorylation (P < 0.05) compared to that of normal pregnant women. Conversely, women with GDM and LGA infants had higher p-Akt (P < 0.001), lower p-AMPKα (P < 0.05), and higher p-mTOR levels (P < 0.05) in the placentas than normal pregnant women. Furthermore, primary cytotrophoblast cells subjected to OGD had lower p-Akt and p-mTOR (both P < 0.05) and higher p-AMPKα levels (P < 0.05) than those cultured under standard conditions, but increasing glucose concentrations had opposite effects on the respective levels. Administering compound C, an AMPK inhibitor, did not significantly affect Akt phosphorylation but partially reversed mTOR phosphorylation. Administering LY294002, an Akt inhibitor, decreased p-mTOR levels, but did not change the levels of total and phosphorylated AMPKα.Conclusion: These results suggest that Akt and AMPK are involved in the regulation of trophoblast mTOR activity in the placentas of pregnancies complicated by FGR and GDM with LGA infants.


BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e022929 ◽  
Author(s):  
Jonas Bacelis ◽  
Julius Juodakis ◽  
Kristina M Adams Waldorf ◽  
Verena Sengpiel ◽  
Louis J Muglia ◽  
...  

ObjectivesTo determine whether uterine distention is associated with human pregnancy duration in a non-invasive observational setting.DesignRetrospective cohort study modelling uterine distention by interaction between maternal height and uterine load.SettingThe study is based on the 1990–2013 population data from all delivery units in Sweden.ParticipantsUncomplicated first pregnancies of healthy Nordic-born mothers with spontaneous onset of labour. Pregnancies were classified as twin (n=2846) or singleton (n=527 868). Singleton pregnancies were further classified as carrying a large for gestational age fetus (LGA, n=24 286) or small for gestational age fetus (SGA, n=33 780).Outcome measuresStatistical interaction between maternal height and uterine load categories (twin vs singleton pregnancies, and LGA vs SGA singleton pregnancies), where the outcome is pregnancy duration.ResultsIn all models, statistically significant interaction was found. Mothers carrying twins had 2.9 times larger positive linear effect of maternal height on gestational age than mothers carrying singletons (interaction p=5e−14). Similarly, the effect of maternal height was strongly modulated by the fetal growth rate in singleton pregnancies: the effect size of maternal height on gestational age in LGA pregnancies was 2.1 times larger than that in SGA pregnancies (interaction p<1e−11). Preterm birth OR was 1.4 when the mother was short, and 2.8 when the fetus was extremely large for its gestational age; however, when both risk factors were present together, the OR for preterm birth was larger than expected, 10.2 (interaction p<0.0005).ConclusionsAcross all classes, maternal height was significantly associated with child’s gestational age at birth. Interestingly, in short-statured women with large uterine load (twins, LGA), spontaneous delivery occurred much earlier than expected. The interaction between maternal height, uterine load size and gestational age at birth strongly suggests the effect of uterine distention imposed by fetal growth on birth timing.


2008 ◽  
Vol 54 (3) ◽  
pp. 550-558 ◽  
Author(s):  
Claudio Chiesa ◽  
John F Osborn ◽  
Cristina Haass ◽  
Fabio Natale ◽  
Marina Spinelli ◽  
...  

Abstract Background: Insulin, growth hormone (GH), and growth factors (insulin-like growth factors [IGFs] and their binding proteins [IGFBPs]) are known to influence fetal growth and also the synthesis/secretion of the recently discovered hormones leptin and ghrelin. Methods: In 153 delivering mothers and their offspring at birth, we prospectively investigated the association between mothers’ and babies’ serum concentrations of ghrelin, leptin, insulin, IGF-1, and IGFBP-3 and neonatal anthropometric characteristics and the growth of the fetus. We also tried to put babies’ serum glucose and GH measurements in this context. Results: Birth weight (BW), birth length, head circumference, and ponderal index (PI) were positively associated with cord IGF-1, IGFBP-3, and leptin and negatively associated with GH. BW was independently associated with maternal stature and prepartum weight, birth length with maternal stature, PI with maternal insulin and prepartum weight, and head circumference with maternal ghrelin. Compared with preterm infants whose development was appropriate for gestational age (AGA), preterm growth-restricted babies displayed alteration in GH-IGF axis (increased GH and low IGF-1 and IGFBP-3 concentrations), low leptin and glucose concentrations, and increased ghrelin concentrations. In large-for-gestational-age (LGA) babies, leptin, IGFBP-3, insulin, and glucose concentrations were significantly higher in asymmetric LGA newborns than in symmetric LGA and AGA newborns. Conclusions: We found relationships between metabolic factors, fetal growth, and anthropometry. Intrauterine growth restriction involved alteration in the fetal GH-IGF axis, with relatively low leptin and glucose concentrations and increased ghrelin concentrations. Leptin, insulin, and IGFBP-3 delineated subtypes of fetal overgrowth.


2020 ◽  
Vol 8 (2) ◽  
pp. e001586
Author(s):  
Emma Assi ◽  
Francesca D'Addio ◽  
Chiara Mandò ◽  
Anna Maestroni ◽  
Cristian Loretelli ◽  
...  

IntroductionGestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy and is associated with development of short-term and long-term complications for newborns, with large-for-gestational-age (LGA) being particularly common. Interestingly, the mechanism behind altered fetal growth in GDM is only partially understood.Research design and methodsA proteomic approach was used to analyze placental samples obtained from healthy pregnant women (n=5), patients with GDM (n=12) and with GDM and LGA (n=5). Effects of altered proteins on fetal development were tested in vitro in human embryonic stem cells (hESCs).ResultsHere, we demonstrate that the placental proteome is altered in pregnant women affected by GDM with LGA, with at least 37 proteins differentially expressed to a higher degree (p<0.05) as compared with those with GDM but without LGA. Among these proteins, 10 are involved in regulating tissue differentiation and/or fetal growth and development, with bone marrow proteoglycan (PRG2) and dipeptidyl peptidase-4 (DPP-4) being highly expressed. Both PRG2 and DPP-4 altered the transcriptome profile of stem cells differentiation markers when tested in vitro in hESCs, suggesting a potential role in the onset of fetal abnormalities.ConclusionsOur findings suggest that placental dysfunction may be directly responsible for abnormal fetal growth/development during GDM. Once established on a larger population, inhibitors of the pathways involving those altered factors may be tested in conditions such as GDM and LGA, in which therapeutic approaches are still lacking.


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