scholarly journals Fetal Gene Variants Associated With Birth Weight Protection in a Native High Altitude Ladakhi Population

2021 ◽  
Author(s):  
Sushil Bhandari ◽  
Padma Dolma ◽  
Mitali Mukerji ◽  
Bhavana Prasher ◽  
Hugh Montgomery ◽  
...  
Keyword(s):  
Birth Weight ◽  
High Altitude ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Principal Component ◽  
Growth Restriction ◽  
Obstetric Outcomes ◽  
Hypoxic Environment ◽  
Show Evidence ◽  
Genomic Regions

Abstract Pathological low birth weight ‘fetal growth restriction’ (FGR) is an important predictor of adverse obstetric outcomes including stillbirth. It is more common amongst native lowlanders when gestating in the hypoxic environment of high altitude, whilst populations who have resided at high altitude for many generations are relatively protected. Genetic study of pregnant populations at high altitude allows for exploration of the hypoxic influence on FGR pathogenesis.Pregnant women were recruited from Sonam Norboo Memorial Hospital, Ladakh between February 2017- January 2019 in this study. Principal component, admixture and genome wide association analysis (GWAS) were applied on umbilical cord blood DNA samples from 316 neonates, to explore ancestry and the genetic influence on low birth weight.Our findings support Tibetan ancestry in the Ladakhi population, with subsequent admixture with neighboring Indo-Aryan populations. Fetal growth protection was evident in Ladakhi neonates. Seven loci from five different genomic regions (ZBTB38, ZFP36L2, HMGA2, CDKAL1, PLCG1) previously associated with birthweight, were likewise similarly associated here. In summary, the Ladakhi population show evidence of enrichment of variants in genes that may help mitigate altitude-associated fetal growth restriction, supporting novel biological pathways and therapeutic targets for FGR, worthy of further investigation.

Fetal growth, high altitude, and evolutionary adaptation: A new perspective

2021 ◽  
Author(s):  
Kathryn Wilsterman ◽  
Zachary A Cheviron
Keyword(s):  
Birth Weight ◽  
High Altitude ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Basic Research ◽  
Growth Restriction ◽  
Physiological Processes ◽  
Health Trajectories ◽  
Fetal Physiology ◽  
New Perspective

Residence at high altitude is consistently associated with low birth weight among placental mammals. This reduction in birth weight influences long-term health trajectories for both the offspring and mother. However, the physiological processes that contribute to fetal growth restriction at altitude are still poorly understood, and thus our ability to safely intervene remains limited. One approach to identify the factors that mitigate altitude-dependent fetal growth restriction is to study populations that are protected from fetal growth restriction through evolutionary adaptations (e.g., high altitude-adapted populations). Here, we examine human gestational physiology at high-altitude from a novel evolutionary perspective that focuses on patterns of physiological plasticity, allowing us to identify (1) the contribution of specific physiological systems to fetal growth restriction and (2) mechanisms that confer protection in highland-adapted populations. Using this perspective, our review highlights two general findings: first, that the beneficial value of plasticity in maternal physiology is often dependent on factors more proximate to the fetus; and second, that our ability to understand the contributions of these proximate factors is currently limited by thin data from altitude adapted populations. Expanding the comparative scope of studies on gestational physiology at high altitude and integrating studies of both maternal and fetal physiology are needed to clarify the mechanisms by which physiological responses to altitude contribute to fetal growth outcomes. The relevance of these questions to clinical, agricultural, and basic research combined with the breadth of the unknown highlight gestational physiology at high altitude as an exciting niche for continued work.

The role of ultrasound in the prediction of birth weight discordance in twin pregnancies: are we there yet?

2018 ◽  
Vol 46 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Ana Raquel Neves ◽  
Filipa Nunes ◽  
Miguel Branco ◽  
Maria do Céu Almeida ◽  
Isabel Santos Silva
Keyword(s):  
Birth Weight ◽  
Fetal Growth ◽  
Predictive Value ◽  
Fetal Growth Restriction ◽  
Predictive Performance ◽  
Growth Restriction ◽  
Operating Characteristics ◽  
Tertiary Center ◽  
Fetal Malformations ◽  
Twin Pregnancies

AbstractObjective:To analyze the accuracy of ultrasound prediction of birth weight discordance (BWD) and the influence of chorionicity and fetal growth restriction (FGR) on ultrasound performance.Methods:Retrospective analysis of 176 twin pregnancies at a Portuguese tertiary center, between 2008 and 2014. Last ultrasound biometry was recorded. Cases with delivery before 24 weeks, fetal malformations, interval between last ultrasound and deliver >3 weeks, twin-to-twin transfusion syndrome and monoamniotic pregnancies were excluded. The accuracy of prediction of BWD was assessed using the area under the receiver-operating characteristics curve (AUC).Results:BWD ≥20% was present in 21.6% of twin pregnancies. EBW had the best predictive performance for BWD (AUC 0.838, 95%CI 0.760–0.916), with a negative predictive value of 86.9% and a positive predictive value of 51.3%. Chorionicity did not influence ultrasound performance. None of the biometric variables analyzed was predictive of BWD in pregnancies without FGR.Conclusion:The accuracy of ultrasound in the prediction of BWD is limited, particularly in pregnancies without fetal growth restriction. Clinical decisions should not rely on BWD alone.

scholarly journals Consensus Definition of Fetal Growth Restriction in Intrauterine Fetal Death: A Delphi Procedure

2020 ◽  
Author(s):  
Irene Maria Beune ◽  
Stefanie Elisabeth Damhuis ◽  
Wessel Ganzevoort ◽  
John Ciaran Hutchinson ◽  
Teck Yee Khong ◽  
...  
Keyword(s):  
Birth Weight ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Fetal Death ◽  
Weight Ratio ◽  
Liver Weight ◽  
Growth Restriction ◽  
Intrauterine Fetal Death ◽  
Consensus Definition ◽  
Definition Of

Context.— Fetal growth restriction is a risk factor for intrauterine fetal death. Currently, definitions of fetal growth restriction in stillborn are heterogeneous. Objectives.— To develop a consensus definition for fetal growth restriction retrospectively diagnosed at fetal autopsy in intrauterine fetal death. Design.— A modified online Delphi survey in an international panel of experts in perinatal pathology, with feedback at group level and exclusion of nonresponders. The survey scoped all possible variables with an open question. Variables suggested by 2 or more experts were scored on a 5-point Likert scale. In subsequent rounds, inclusion of variables and thresholds were determined with a 70% level of agreement. In the final rounds, participants selected the consensus algorithm. Results.— Fifty-two experts participated in the first round; 88% (46 of 52) completed all rounds. The consensus definition included antenatal clinical diagnosis of fetal growth restriction OR a birth weight lower than third percentile OR at least 5 of 10 contributory variables (risk factors in the clinical antenatal history: birth weight lower than 10th percentile, body weight at time of autopsy lower than 10th percentile, brain weight lower than 10th percentile, foot length lower than 10th percentile, liver weight lower than 10th percentile, placental weight lower than 10th percentile, brain weight to liver weight ratio higher than 4, placental weight to birth weight ratio higher than 90th percentile, histologic or gross features of placental insufficiency/malperfusion). There was no consensus on some aspects, including how to correct for interval between fetal death and delivery. Conclusions.— A consensus-based definition of fetal growth restriction in fetal death was determined with utility to improve management and outcomes of subsequent pregnancies.

scholarly journals Maternal risk factors and perinatal outcomes in fetal growth restriction using obstetric Doppler in South Kerala, India

2018 ◽  
Vol 8 (1) ◽  
pp. 6
Author(s):  
Heera Shenoy T. ◽  
Sonia X. James ◽  
Sheela Shenoy T.
Keyword(s):  
Risk Factors ◽  
Birth Weight ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Perinatal Outcomes ◽  
Growth Restriction ◽  
P Value ◽  
Maternal Risk Factors ◽  
Maternal Risk ◽  
The Mean

Background: Fetal Growth Restriction (FGR) is the single largest contributing factor to perinatal morbidity in non-anomalous foetuses. Synonymous with Intrauterine Growth Restriction (IUGR), it is defined as an estimated fetal weight less than the10th percentile. Obstetric Doppler has helped in early detection and timely intervention in babies with FGR with significant improvements in perinatal outcomes.  Hence, authors evaluated the maternal risk factors and diagnosis-delivery intervals and perinatal outcomes in FGR using Doppler.Methods: This research conducted in a tertiary care hospital in South Kerala included 82 pregnant women who gave birth to neonates with birth weight less than the 10th percentile over a period of1 year (Jan 1, 2017-Dec 31, 2017). Socio-demographic, maternal risk, Diagnosis- delivery interval in FGR and neonatal morbidities were studied.Results: Mean GA at diagnosis in weeks was 34.29 and 35.19 respectively for abnormal and normal Doppler respectively (p value-0.032). The mean birthweight in Doppler abnormal FGR was 272.34 g lesser than in Doppler normal group (p value-0.001). Growth restricted low birth weight neonates had Doppler   pattern abnormalities (p value-0.0009). FGR <3rd percentile and AFI <5 had abnormal Doppler (OR:6.7). Abnormal biophysical profile (OR:14) and Non-Reactive NST (OR:3.5) correlated with abnormal Doppler. Growth restricted with normal Doppler had shorter NICU stays than with abnormalities (p value-0.003). Term FGR went home early than early preterm. (p value-0.001).Conclusions: Abnormal Doppler velocimetry is significantly associated with earlier FGR detection, shorter decision- delivery interval, reduction in the mean birthweight and longer NICU stay. Hence, Umbilical artery Doppler and Cerebroplacental index is an integral part of in-utero fetal surveillance to identify impending fetal hypoxia, appropriate management, optimising the timing of delivery and improve perinatal health in FGR.

Early growth outcomes in very low birth weight infants with bronchopulmonary dysplasia or fetal growth restriction

2020 ◽  
Vol 88 (4) ◽  
pp. 601-604
Author(s):  
Jennifer Check ◽  
Elizabeth T. Jensen ◽  
Joseph A. Skelton ◽  
Walter T. Ambrosius ◽  
T. Michael O’Shea
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Bronchopulmonary Dysplasia ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Very Low Birth Weight ◽  
Early Growth ◽  
Growth Restriction ◽  
Low Birth Weight Infants ◽  
Growth Outcomes

scholarly journals Prediction of late-onset fetal growth restriction using a combined first- and second-trimester screening model in South Chinese infants: a retrospective study

2019 ◽  
Author(s):  
Haiqing Zheng ◽  
Yan Feng ◽  
Jiexin Zhang ◽  
Kuanrong Li ◽  
Huiying Liang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Birth Weight ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Detection Rate ◽  
Prediction Models ◽  
Late Onset ◽  
Growth Restriction ◽  
Abdominal Circumference ◽  
Second Trimester

Abstract Background Prediction models for early and late fetal growth restriction (FGR) have been established in many high-income countries. However, prediction models for late FGR in China are limited. This study aimed to develop a simple combined first- and second-trimester prediction model for screening late-onset FGR in South Chinese infants.Methods This retrospective study included 2258 women who had singleton pregnancies and received routine ultrasound scans. Late-onset FGR was defined as a birth weight < the 10th percentile plus abnormal Doppler indices and/or a birth weight below the 3rd percentile after 32 weeks, regardless of the Doppler status. Multivariate logistic regression was used to develop a prediction model.Results Ninety-three fetuses were identified as late-onset FGR. The significant predictors for late-onset FGR were maternal age, height, weight, and medical history; the second-trimester head circumference (HC)/abdominal circumference (AC) ratio; and the estimated fetal weight (EFW). This model achieved a detection rate (DR) of 52.6% for late-onset FGR at a 10% false positive rate (FPR) (area under the curve (AUC): 0.80, 95%CI 0.76-0.85).Conclusions A multivariate model combining first- and second-trimester default tests can detect 52.6% of cases of late-onset FGR. Further studies with more screening markers are needed to improve the detection rate.

scholarly journals Does Pentaerytrithyltetranitrate reduce fetal growth restriction in pregnancies complicated by uterine mal-perfusion? Study protocol of the PETN-study: a randomized controlled multicenter-trial

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
T. Groten ◽  
◽  
T. Lehmann ◽  
E. Schleußner
Keyword(s):  
Birth Weight ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Uterine Artery ◽  
Therapeutic Option ◽  
Multicenter Trial ◽  
Growth Restriction ◽  
Organic Nitrate ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Uterine Artery Doppler

Abstract Background Affecting approximately 10% of pregnancies, fetal growth restriction (FGR), is the most important cause of perinatal mortality and morbidity. Impaired placental function and consequent mal-perfusion of the placenta is the leading cause of FGR. Although, screening for placental insufficiency based on uterine artery Doppler measurement is well established, there is no treatment option for pregnancies threatened by FGR. The organic nitrate pentaerithrityl tetranitrate (PETN) is widely used for the treatment of cardiovascular disease and has been shown to have protective effects on human endothelial cells. In a randomized placebo controlled pilot-study our group could demonstrate a risk reduction of 39% for the development of FGR, and FGR or death, by administering PETN to patients with impaired uterine artery Doppler at mid gestation. To confirm these results a prospective randomized placebo controlled double-blinded multicentre trial was now initiated. Method The trial has been initiated in 14 centres in Germany. Inclusion criteria are abnormal uterine artery Doppler, defined by mean PI > 1.6, at 190 to 226 weeks of gestation in singleton pregnancies. Included patients will be monitored in 4-week intervals. Primary outcome measures are development of FGR (birth weight < 10th percentile), severe FGR (birth weight < 3rd centile) and perinatal death. Placental abruption, birth weight below the 3rd, 5th and 10th centile, development of FGR requiring delivery before 34 weeks` gestation, neonatal intensive care unit admission, and spontaneous preterm delivery < 34 weeks` and 37 weeks` gestation will be assessed as secondary endpoints. Patient enrolment was started in August 2017. Results are expected in 2020. Discussion During the past decade therapeutic agents with possible perfusion optimizing potential have been evaluated in clinical trials to treat FGR. Meta-analysis and sub-analysis of trials targeting preeclampsia revealed ASS to have a potential in reducing FGR. Phosphodiesterase-type-5 inhibitors have recently been tested in a worldwide RCT for therapy of established FGR, failing to show an effect on neonatal outcome. The ongoing multicenter trial will, by confirming our previous results, finally provide a therapeutic option in cases at risk for FGR. Trial registration DRKS00011374 registered at September 29th, 2017 and NCT03669185, registered September 13th, 2018.

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