Fetal programming: the perspective of single and twin pregnancies

2005 ◽  
Vol 17 (3) ◽  
pp. 379 ◽  
Author(s):  
Michael J. Davies
Keyword(s):  
Chronic Disease ◽  
Fetal Growth ◽  
Low Birthweight ◽  
Multiple Pregnancy ◽  
Experimental Studies ◽  
Later Life ◽  
Growth Restriction ◽  
Physiological Adaptation ◽  
Increased Risk ◽  
Twin Pregnancies

Multiple pregnancy is associated with increased risk of adverse consequences for both mother and fetus(es), including increased rates of maternal hypertension and pre-eclampsia, spontaneous abortion, Caesarean delivery, low birthweight, birth prematurity, perinatal mortality, admission to neonatal intensive care and extended length of care, respiratory distress, cerebral palsy, developmental delay, contact with disability services and mortality to age 5 years. Premature birth, which affects 97% of triplets and 53.3% of twins in Australia, is not the sole factor involved. The rate of multiple pregnancy in Australia is 1.7%. This compares to 22.1% for pregnancies resulting from assisted reproduction technology (ART). As a result, 21.8% of babies born from ART are from a multiple pregnancy, in comparison to the USA where the majority of babies born from ART are from a multiple pregnancy. Additionally, the population rate of multiple births is rising due to the more frequent use of ART and continued multi-embryo transfers, which is operating against a background of rising implantation rates within ART clinics. Twins have been of interest from a programming perspective. However, analysis of associations between crude birthweight and subsequent metabolic risk factors or mortality in adulthood from chronic disease indicate that adaptations in pregnancy to support multi-fetal growth are not identical to fetal growth restriction in singleton pregnancies. Indeed, the process of ‘maternal constraint’ is incompletely understood and confounds such comparisons. From a programming perspective, it is a challenge to identify in twin pregnancies the transition from physiological adaptation to pathological growth restriction. Growth disparity between twins has been more illuminating of subtle adverse effects for the smaller of twin pairs in both blood pressure and insulin resistance in adulthood. Interestingly, these effects can be observed in both dizygotic and to a lesser degree in monozygotic twins, which indicates a role for both genetic and environmental factors in these measures. This suggests that, consistent with experimental studies in other species, the relationship between impaired growth in utero and chronic disease in later life is not simply mediated by a common genetic pathway.

scholarly journals Association of an Increased Risk of Pre-Eclampsia (PE) and Fetal Growth Restriction (FGR) in Singleton and Twin Pregnancies with Female Fetuses

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Shi-Lei Bi ◽  
Li-Zi Zhang ◽  
Zhi-Jian Wang ◽  
Jing-Man Tang ◽  
Su-Shan Xie ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Increased Risk ◽  
Twin Pregnancies

scholarly journals Modulation of Placental Gene Expression in Small-for-Gestational-Age Infants

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 80 ◽  
Author(s):  
Jessica L. O’Callaghan ◽  
Vicki L. Clifton ◽  
Peter Prentis ◽  
Adam Ewing ◽  
Yvette D. Miller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fetal Growth ◽  
Current Literature ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Placental Tissue ◽  
Later Life ◽  
Growth Restriction ◽  
Growth Potential ◽  
Increased Risk

Small-for-gestational-age (SGA) infants are fetuses that have not reached their genetically programmed growth potential. Low birth weight predisposes these infants to an increased risk of developing cardiovascular, metabolic and neurodevelopmental conditions in later life. However, our understanding of how this pathology occurs is currently incomplete. Previous research has focused on understanding the transcriptome, epigenome and bacterial signatures separately. However, we hypothesise that interactions between moderators of gene expression are critical to understanding fetal growth restriction. Through a review of the current literature, we identify that there is evidence of modulated expression/methylation of the placental genome and the presence of bacterial DNA in the placental tissue of SGA infants. We also identify that despite limited evidence of the interactions between the above results, there are promising suggestions of a relationship between bacterial signatures and placental function. This review aims to summarise the current literature concerning fetal growth from multiple avenues and propose a novel relationship between the placental transcriptome, methylome and bacterial signature that, if characterised, may be able to improve our current understanding of the placental response to stress and the aetiology of growth restriction.

scholarly journals Long term alterations of growth after antenatal steroids in preterm twin pregnancies

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Thorsten Braun ◽  
Vivien Filleböck ◽  
Boris Metze ◽  
Christoph Bührer ◽  
Andreas Plagemann ◽  
...  
Keyword(s):  
Early Childhood ◽  
Disease Risk ◽  
Later Life ◽  
Ponderal Index ◽  
Childhood Growth ◽  
Antenatal Steroids ◽  
Increased Risk ◽  
Infancy And Early Childhood ◽  
Twin Pregnancies

AbstractObjectivesTo compare the long-term effects of antenatal betamethasone (ANS, ≤16 mg, =24 mg and >24 mg) in twins on infant and childhood growth.MethodsA retrospective cohort follow up study among 198 twins after ANS including three time points: U1 first neonatal examination after birth and in the neonatal period; U7 examination from the 21st to the 24th month of life and U9 examination from the 60th to the 64th month of life using data from copies of the children’s examination booklets. Inclusion criteria are twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to ANS between 23+5 and 33+6 weeks. Outcome measures are dosage-dependent and sex-specific effects of ANS on growth (body weight, body length, head circumference, body mass index and ponderal index) up to 5.3 years.ResultsOverall, 99 live-born twin pairs were included. Negative effects of ANS on fetal growth persisted beyond birth, altered infant and childhood growth, independent of possible confounding factors. Overall weight percentile significantly decreased between infancy and early childhood by 18.8%. Birth weight percentiles significantly changed in a dose dependent and sex specific manner, most obviously in female-female and mixed pairs. The ponderal index significantly decreased up to 42.9%, BMI index increased by up to 33.8%.ConclusionsANS results in long-term alterations in infant and childhood growth. Changes between infancy and early childhood in ponderal mass index and BMI, independent of dose or twin pair structure, might indicate an ANS associated increased risk for later life disease.SynopsisFirst-time report on long-term ANS administration growth effects in twin pregnancies, showing persisting alterations beyond birth in infant and childhood growth up to 5.3 years as potential indicator of later life disease risk.

scholarly journals Growth patterns of monochorionic twin pregnancies complicated by type‐3 selective fetal growth restriction

2021 ◽  
Author(s):  
S. Shinar ◽  
W. Xing ◽  
L. Lewi ◽  
F. Slaghekke ◽  
Y. Yinon ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Patterns ◽  
Growth Restriction ◽  
Monochorionic Twin ◽  
Type 3 ◽  
Twin Pregnancies

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.

Spontaneous loss of a co-twin and the risk of birth defects after assisted conception

2016 ◽  
Vol 7 (6) ◽  
pp. 678-684 ◽  
Author(s):  
M. J. Davies ◽  
A. R. Rumbold ◽  
M. J. Whitrow ◽  
K. J. Willson ◽  
W. K. Scheil ◽  
...  
Keyword(s):  
Birth Defects ◽  
Pregnancy Loss ◽  
Multiple Pregnancy ◽  
Fetal Loss ◽  
South Australia ◽  
Increased Risk ◽  
Study Population ◽  
Infertility Patients ◽  
Twin Pregnancies ◽  
Singleton Pregnancies

The study of very early pregnancy loss is impractical in the general population, but possible amongst infertility patients receiving carefully monitored treatments. We examined the association between fetal loss and the risk of birth defects in the surviving co-twin in a retrospective cohort study of infertility patients within an infertility clinic in South Australia from January 1986 to December 2002, linked to population registries for births, terminations and birth defects. The study population consisted of a total of 5683 births. Births from singleton pregnancies without loss were compared with survivors from (1) pregnancies with an empty fetal sac at 6–8 weeks after embryo transfer, (2) fetal loss subsequent to 8-week ultrasound and (3) multiple pregnancy continuing to birth. Odds ratios (OR) for birth defects were calculated with adjustment for confounders. Amongst infertility patients, the prevalence of birth defects was 7.9% for all twin pregnancies without fetal loss compared with 14.6% in pregnancies in which there had been an empty sac at ultrasound, and 11.6% for pregnancies with fetal loss after 6–8 weeks. Compared with singleton pregnancies without loss, the presence of an empty sac was associated with an increased risk of any defect (OR=1.90, 95% confidence intervals (CI)=1.09–3.30) and with multiple defects (OR=2.87, 95% CI=1.31–6.28). Twin pregnancies continuing to birth without loss were not associated with an overall increased prevalence of defects. We conclude that the observed loss of a co-twin by 6–8 weeks of pregnancy is related to the risk of major birth defects in the survivor.

scholarly journals Epigenetics and DOHaD: from basics to birth and beyond

2017 ◽  
Vol 8 (5) ◽  
pp. 513-519 ◽  
Author(s):  
T. Bianco-Miotto ◽  
J. M. Craig ◽  
Y. P. Gasser ◽  
S. J. van Dijk ◽  
S. E. Ozanne
Keyword(s):  
Dna Methylation ◽  
Chronic Disease ◽  
Chronic Diseases ◽  
Early Life ◽  
Later Life ◽  
Metabolic Health ◽  
Number Of Children ◽  
Early Life Environment ◽  
Increased Risk ◽  
Early Life Exposures

Developmental origins of health and disease (DOHaD) is the study of how the early life environment can impact the risk of chronic diseases from childhood to adulthood and the mechanisms involved. Epigenetic modifications such as DNA methylation, histone modifications and non-coding RNAs are involved in mediating how early life environment impacts later health. This review is a summary of the Epigenetics and DOHaD workshop held at the 2016 DOHaD Society of Australia and New Zealand Conference. Our extensive knowledge of how the early life environment impacts later risk for chronic disease would not have been possible without animal models. In this review we highlight some animal model examples that demonstrate how an adverse early life exposure results in epigenetic and gene expression changes that may contribute to increased risk of chronic disease later in life. Type 2 diabetes and cardiovascular disease are chronic diseases with an increasing incidence due to the increased number of children and adults that are obese. Epigenetic changes such as DNA methylation have been shown to be associated with metabolic health measures and potentially predict future metabolic health status. Although more difficult to elucidate in humans, recent studies suggest that DNA methylation may be one of the epigenetic mechanisms that mediates the effects of early life exposures on later life risk of obesity and obesity related diseases. Finally, we discuss the role of the microbiome and how it is a new player in developmental programming and mediating early life exposures on later risk of chronic disease.

Maternal Carbenoxolone Treatment Lowers Birthweight and Induces Hypertension in the Offspring of Rats Fed a Protein-Replete Diet

1997 ◽  
Vol 93 (5) ◽  
pp. 423-429 ◽  
Author(s):  
Simon C. Langley-Evans
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Fetal Growth ◽  
Low Birthweight ◽  
Control Diet ◽  
Later Life ◽  
Hydroxysteroid Dehydrogenase ◽  
Fetal Exposure ◽  
Low Protein ◽  
Protein Diets

1. In the rat low birthweight and raised systolic blood pressure are the consequence of fetal exposure to maternal low protein diets. Nutritional down-regulation of the placental isoform of 11β-hydroxysteroid dehydrogenase, which may increase exposure of the fetus to maternal glucocorticoids, has been suggested to underlie effects of low protein diets on fetal growth and blood pressure. 2. Pregnant rats were fed control (18% casein) or low protein (9% casein) diets throughout gestation. Animals fed the control diet were injected with carbenoxolone, an inhibitor of 11β-hydroxysteroid dehydrogenase. Injections were administered either throughout pregnancy (days 0–22), or targeted to specific periods in early (days 0–7), mid- (days 8–14) or late (days 15–22) gestation. 3. Exposure to a low protein diet reduced birthweight and at 4 weeks of age systolic blood pressure was significantly elevated in the rats exposed to low protein. These hypertensive animals had small kidneys in proportion to body weight. 4. Fetal exposure to carbenoxolone at any period in gestation resulted in lower weight at birth. In rats exposed to the inhibitor over days 8–14, 15–22 or 0–22 systolic blood pressure at 4 weeks was significantly higher than in control animals. The greatest elevation of pressure was associated with carbenoxolone treatment in late (days 15–22) gestation. Animals with carbenoxolone-induced hypertension did not exhibit evidence of retarded renal growth. 5. Increased fetal exposure to maternal glucocorticoids impairs fetal growth and programmes elevated blood pressure in later life.

scholarly journals Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Samantha C. Lean ◽  
Alexander E. P. Heazell ◽  
Mark R. Dilworth ◽  
Tracey A. Mills ◽  
Rebecca L. Jones
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Maternal Age ◽  
Advanced Maternal Age ◽  
Growth Restriction ◽  
Placental Dysfunction ◽  
Increased Risk
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