Are Fetal and Neonatal Growth Curves Different in Predicting the Impact of Intrauterine Growth Restriction on Neonatal Mortality and Morbidity?

Abstract Chorionic somatomammotropin (CSH) is one of the most abundant hormones produced by the sheep placenta, yet the exact function of CSH has been elusive. Previously we reported the use of in vivo RNA interference (RNAi) to assess the impact of CSH deficiency on placental and fetal growth in sheep. Near-term (135 dGA), there are two distinct CSH RNAi phenotypes: 1) pregnancies with intrauterine growth restriction (IUGR), and 2) pregnancies with normal fetal and placental weights. This study describes physiological changes in the latter phenotype. To generate the CSH RNAi pregnancies, the trophectoderm of hatched blastocysts (9 dGA) were infected with lentiviral-constructs expressing either a scrambled control (NTS) or CSH-specific shRNA (CSH RNAi), prior to transfer into synchronized recipient ewes. At 120 dGA, 6 NTS and 6 CSH RNAi pregnancies were fitted with maternal and fetal catheters. Uterine and umbilical blood flows were measured utilizing the 3H2O transplacental diffusion technique at 132 dGA, and nutrient uptakes were calculated by the Fick principle. Resulting data were analyzed by Student’s t-test and significance was set at P ≤ 0.05. CSH RNAi tended (P ≤ 0.10) to reduce placentome weight with no effect on fetal weight. Absolute (ml/min) and relative (ml/min/kg fetus) uterine blood flows were reduced (P ≤ 0.05) in CSH RNAi pregnancies, but umbilical flows were not impacted. The uterine artery-to-vein glucose gradient (mmol/l) was significantly (P ≤ 0.05) increased, whereas the gradients for taurine and glycine were reduced (P ≤ 0.05). Uteroplacental glucose uptake (mmol/min/kg placenta) was increased 27% (P ≤ 0.05), whereas umbilical glucose uptake (mmol/min/kg fetus) was reduced 13%. This cohort demonstrates that even in the absence of IUGR, CSH deficiency has significant physiological ramifications, and the investigation of CSH RNAi pregnancies exhibiting both IUGR and non-IUGR phenotypes may help determine the direct effects of CSH and its potential impact on fetal programming. Supported by NIH R01 HD093701.

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Understanding intrauterine growth restriction (IUGR): a review

Journal of Biomedical Sciences ◽

10.3126/jbs.v2i4.15426 ◽

2016 ◽

Vol 2 (4) ◽

pp. 31-37 ◽

Cited By ~ 1

Author(s):

Pankaj Verma ◽

Hema Chaudhary

Keyword(s):

Intrauterine Growth Restriction ◽

Normal Growth ◽

Bed Rest ◽

Growth Restriction ◽

Growth Potential ◽

Biomedical Sciences ◽

Pharmacological Management ◽

Mortality And Morbidity ◽

Intrauterine Growth ◽

Aryl Hydrocarbon

Intrauterine Growth Restriction (IUGR) is defined as the inability of a fetus to gain the normal growth potential due to maternal-placental-fetal factors. These factors mainly involve metabolic disorders, infections, substance abuse and exposure to harmful substances. Incidence of IUGR is higher in developing countries. Proper diagnosis at suitable time is necessary for proper treatment and management. Although, the mechanism is not clear but oxidative stress, immunological factors, aryl hydrocarbon receptor and adduct formation are some pathways which are involved in IUGR. The aftermaths of IUGR involves post-birth complications, perinatal mortality and morbidity. Therefore, management and treatment involves use of both pharmacological (Tocolytics, Corticosteroids, antibiotics) and non-pharmacological methods (bed rest, cerclage). This review highlights the possible risk factors, mechanisms, other biochemical pathways involved, as well as pharmacological and non-pharmacological management of IUGR.Journal of Biomedical Sciences. 2015;2(4):31-37

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Associations of Intrauterine Growth Restriction Among Term Infants and Maternal Pregnancy Intendedness, Initial Happiness About Being Pregnant, and Sense of Control

PEDIATRICS ◽

10.1542/peds.111.s1.1171 ◽

2003 ◽

Vol 111 (Supplement_1) ◽

pp. 1171-1175

Author(s):

Sharon Durousseau ◽

Gilberto F. Chavez

Keyword(s):

Confidence Interval ◽

Psychosocial Factors ◽

Intrauterine Growth Restriction ◽

Odds Ratio ◽

Growth Restriction ◽

Sense Of Control ◽

Term Infants ◽

Mortality And Morbidity ◽

Intrauterine Growth ◽

Pregnancy Intendedness

Objective. Term infants (≥37 weeks’ gestation) who weigh <2500 g have intrauterine growth restriction (IUGR) and have a higher risk of mortality and morbidity. Little is known about how psychosocial factors affect the risk of IUGR. We examined the association between IUGR and maternal pregnancy intendedness, initial happiness about becoming pregnant, and maternal sense of control. Methods. We analyzed data from a survey of California mothers aged ≥15 years with term live births in 1999 and 2000 (N = 5961). Mothers were asked about pregnancy intendedness before pregnancy, initial happiness about becoming pregnant, and maternal sense of control, assessed by a standardized scale. We examined the association of having an infant with IUGR and these factors in univariate and multivariate analyses. Results. Mothers with low sense of control (3.0%) and average sense of control (2.7%) were more likely to have an infant with IUGR than mothers with high sense of control (1.8%; odds ratio: 1.8; 95% confidence interval: 1.2–2.9; and odds ratio: 1.6; 95% confidence interval: 1.0–2.5). After multivariate analysis, we found no significant association between sense of control and IUGR. We also found no significant association between IUGR and pregnancy intendedness and happiness about becoming pregnant. Conclusions. We found no statistically significant association between IUGR and maternal pregnancy intendedness, initial happiness about becoming pregnant, and maternal sense of control. Although research should continue to explore associations between psychosocial factors and IUGR, prenatal care programs should focus on known risk factors for IUGR.

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338: How to define intrauterine-growth-restriction – based on sonographic growth curves or neonatal birthweight growth curves?

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2018.11.359 ◽

2019 ◽

Vol 220 (1) ◽

pp. S236-S237

Author(s):

Marva Bergman ◽

Alon Z. Sapir ◽

Izzat Khayyat ◽

Rivka Farkash ◽

Arnon Samueloff ◽

...

Keyword(s):

Intrauterine Growth Restriction ◽

Growth Curves ◽

Growth Restriction ◽

Intrauterine Growth

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Whey Versus Casein as a Protein Source during the Weaning Period: Impact on Growth and Later Adiposity and Glucose Homeostasis in a Rat Model of Intrauterine Growth Restriction

Nutrients ◽

10.3390/nu12113399 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3399

Author(s):

Yasaman Shahkhalili ◽

Florence Blancher-Budin ◽

Cathriona Monnard ◽

Julie Moulin ◽

José Sanchez-Garcia ◽

...

Keyword(s):

Glucose Homeostasis ◽

Intrauterine Growth Restriction ◽

Early Life ◽

Growth Restriction ◽

Protein Source ◽

Intrauterine Growth ◽

Populations At Risk ◽

Ad Libitum ◽

The Impact

The impact of early life protein source (whey vs. casein) on short- and long-term glucose homeostasis and adiposity is unknown and was investigated in this study. At the end of the suckling period, non-IUGR (intrauterine growth restriction) and IUGR pups were separated from dams and were randomized into four groups. From age 21–49 days, non-IUGR and IUGR pups were fed ad-libitum chow or a semi-synthetic diet (20% from protein; casein or whey) and from age 50–199 days, all groups were fed ad-libitum chow. Food intake, body composition, glucose, and insulin homeostasis were assessed. Among the chow groups, IUGR had slower growth and higher fasting glucose at age 42 days, as well as higher fasting and AUC glucose at age 192 days relative to non-IUGR. The whey IUGR group had a slower growth rate and higher fasting glycemia in early life (age 21–49 days) and higher HOMA-IR later in life (age 120–122 and 190–192 days) relative to casein IUGR. This study shows the potential advantage of casein relative to whey during weaning on short term energy intake, growth, and glucose homeostasis in an IUGR model and reveals, for the first time, its long term impact on insulin sensitivity, which may have implications for later metabolic health, particularly in small-for-gestational-age populations at risk of type 2 diabetes.

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Vitamin D deficiency and impaired placental function: potential regulation by glucocorticoids?

Reproduction ◽

10.1530/rep-16-0647 ◽

2017 ◽

Vol 153 (5) ◽

pp. R163-R171 ◽

Cited By ~ 13

Author(s):

Nathanael Yates ◽

Rachael C Crew ◽

Caitlin S Wyrwoll

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Intrauterine Growth Restriction ◽

Adverse Outcomes ◽

Growth Restriction ◽

Placental Function ◽

Maternal Vitamin ◽

Intrauterine Growth ◽

The Impact ◽

Established Role

Maternal vitamin D deficiency has been implicated in a range of pregnancy complications including preeclampsia, preterm birth and intrauterine growth restriction. Some of these adverse outcomes arise from alterations in placental function. Indeed, vitamin D appears critical for implantation, inflammation, immune function and angiogenesis in the placenta. Despite these associations, absence of the placental vitamin D receptor in mice provokes little effect. Thus, interactions between maternal and fetal compartments are likely crucial for instigating adverse placental changes. Indeed, maternal vitamin D deficiency elicits changes in glucocorticoid-related parameters in pregnancy, which increase placental and fetal glucocorticoid exposure. Asin uteroglucocorticoid excess has a well-established role in eliciting placental dysfunction and fetal growth restriction, this review proposes that glucocorticoids are an important consideration when understanding the impact of vitamin D deficiency on placental function and fetal development.

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The impact of intrauterine growth restriction on cytochrome P450 enzyme expression and activity

Placenta ◽

10.1016/j.placenta.2020.07.012 ◽

2020 ◽

Vol 99 ◽

pp. 50-62

Author(s):

Grace M. McBride ◽

Michael D. Wiese ◽

Jia Yin Soo ◽

Jack R.T. Darby ◽

Mary J. Berry ◽

...

Keyword(s):

Cytochrome P450 ◽

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Cytochrome P450 Enzyme ◽

Enzyme Expression ◽

Intrauterine Growth ◽

P450 Enzyme ◽

The Impact ◽

Expression And Activity

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The impact of maternal parameters on intrauterine growth restriction

Perinatologia ◽

10.26416/peri.1.1.2017.470 ◽

2017 ◽

Vol 1 (1) ◽

pp. 6

Author(s):

Monica Mihaela Cîrstoiu ◽

Natalia Turcan ◽

Roxana-Elena Bohîlţea ◽

Octavian Munteanu ◽

Oana Bodean ◽

...

Keyword(s):

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Intrauterine Growth ◽

The Impact

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Analysis of fetal growth restriction in pregnancy in subjects attending in an obstetric clinic of a tertiary care teaching hospital

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20180876 ◽

2018 ◽

Vol 7 (3) ◽

pp. 973

Author(s):

Ashish Seal ◽

Arup Dasgupta ◽

Mousumi Sengupta ◽

Rinini Dastider ◽

Sukanta Sen

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Intrauterine Growth Restriction ◽

Tertiary Care ◽

Growth Restriction ◽

Growth Potential ◽

Crown Rump Length ◽

Mortality And Morbidity ◽

Intrauterine Growth ◽

In Pregnancy

Background: Intrauterine growth restriction (IUGR) is defined as fetal growth less than the normal growth potential of a specific infant because of genetic or environmental factors. Fetal growth restriction or intrauterine growth restriction is one of the leading causes of perinatal mortality and morbidity in newborns. Fetal growth restriction is a complex multifactorial condition resulting from several fetal and maternal disorders. Objective of present study was to find out incidence of IUGR and assessment and evaluation of different important changes in IUGR.Methods: Women who attended the Obstetric OPD in their 1st trimester of pregnancy and those who were thought would be able to visit the antenatal clinic for their fortnightly check-up regularly were screened for intrauterine foetal growth retardation. Women with irregular and uncertain menstrual history and where the 1st trimester USG foetal crown rump length did not corroborate with the menstrual gestational age were excluded from this study.Results: Incidence of IUGR was 18.2% and 84% were found to be asymmetrical. IUGR was found to be double among primigravids and women above 30 years. It had been observed that IUGR was associated with certain conditions like short stature (52%), pregnancy induced hypertension (24%) and anaemia (12%).Conclusions: Thus, early USG screening along with robust screening for maternal BMI, nutritional status, and anaemia can assist the obstetric team in providing early diagnosis, prompt intervention, and better outcome in pregnancy with fetal growth restriction.

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The effect of hypoxia-induced intrauterine growth restriction on renal artery function

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174412000268 ◽

2012 ◽

Vol 3 (5) ◽

pp. 333-341 ◽

Cited By ~ 6

Author(s):

M. T. C. Verschuren ◽

J. S. Morton ◽

A. Abdalvand ◽

Y. Mansour ◽

C. F. Rueda-Clausen ◽

...

Keyword(s):

Renal Artery ◽

Intrauterine Growth Restriction ◽

Vascular Function ◽

In Utero ◽

Growth Restriction ◽

Dependent Manner ◽

Intrauterine Growth ◽

Kidney Morphology ◽

Renal Senescence ◽

The Impact

The risk of developing cardiovascular diseases is known to begin before birth and the impact of the intrauterine environment on subsequent adult health is currently being investigated from many quarters. Following our studies demonstrating the impact of hypoxiain uteroand consequent intrauterine growth restriction (IUGR) on the rat cardiovascular system, we hypothesized that changes extend throughout the vasculature and alter function of the renal artery. In addition, we hypothesized that hypoxia induces renal senescence as a potential mediator of altered vascular function. We demonstrated that IUGR females had decreased responses to the adrenergic agonist phenylephrine (PE; pEC506.50 ± 0.05 controlv. 6.17 ± 0.09 IUGR,P< 0.05) and the endothelium-dependent vasodilator methylcholine (MCh;Emax89.8 ± 7.0% controlv. 41.0 ± 6.5% IUGR,P< 0.001). In IUGR females, this was characterised by increased basal nitric oxide (NO) modulation of vasoconstriction (PE pEC506.17 ± 0.09 IUGRv. 6.42 ± 0.08 in the presence of the NO synthase inhibitorN-nitro-l-arginine methyl ester hydrochloride (l-NAME;P< 0.01) but decreased activated NO modulation (no change in MCh responses in the presence ofl-NAME), respectively. In contrast, IUGR males had no changes in PE or MCh responses but demonstrated increased basal NO (PE pEC506.29 ± 0.06 IUGRv. 6.42 ± 0.12 plusl-NAME,P< 0.01) and activated NO (Emax37.8 ± 9.4% controlv. −0.8 ± 13.0% plusl-NAME,P< 0.05) modulation. No significant changes were found in gross kidney morphology, proteinuria or markers of cellular senescence in either sex. In summary, renal vascular function was altered by hypoxiain uteroin a sex-dependent manner but was unlikely to be mediated by premature renal senescence.

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