Low birth weight,intrauterine growth-retarded,and pre-term infants

Low birth weight, intrauterine growth retardation, and prematurity are overwhelming risk factors associated with infant mortality and morbidity. The lack of efficacious prenatal screening tests for these three outcomes illuminates the problems inherent in bivariate estimates of association. A biocultural strategy for research is presented, integrating societal and familial levels of analysis with the metabolic, immune, vascular, and neuroendocrine systems of the body. Policy decisions, it is argued, need to be based on this type of biocultural information in order to impact the difficult-to-change problems of low birth weight, intrauterine growth retardation, and prematurity. The analysis and writing of this study was funded, in part, by a grant from the National Institute of Child Health and Human Development (NICHD RO1 HD 20511). Troy D. Abell is associate professor of anthropology and adjunct associate professor of family medicine at the University of Oklahoma. His major interests are in the biocultural determinants of fetal growth and the epistemologic issues inherent in statistical reasoning in scientific inference and decision analysis.     

Variation in early neonatal mortality for different types of fetal growth retardation

Birth and first-48-hr death records were analyzed for 10,024 liveborn infants in Mexico City and 12,786 liveborn infants in Santa Cruz, Bolivia. The objective of the analysis was to characterize the early postnatal mortality rates for different types of fetal growth retardation and prematurity. Infants who were delivered prior to 37 weeks of gestation had 23-100 times the mortality risk of infants born at full term and normal weight. Light-for-gestational-age infants (birth weight less than 2,900 g) were further divided into proportionately growth-retarded with normal Rohrer's index (weight/height) and disproportionately growth-retarded with low Rohrer's index. The proportionately growth-retarded infant had nearly twice the mortality of the full-term, appropriate-weight infants, whereas the disproportionately growth-retarded infants had 2.9-5.7 times the mortality rate of the full-term, appropriate-weight infants. There were some differences between samples in mortality rates and prevalence of the different classes of small infants, but the pattern of mortality within samples was consistent between samples.     

Hypothalamus integrity and appetite regulation in low birth weight rats reared artificially on a high-protein milk formula

High-protein (HP) milk formulas are routinely used in infants born with a low birth weight (LBW) to enhance growth and ensure a better verbal IQ development. Indirect evidence points to a link between an HP intake during early life and the prevalence of obesity in later life. We hypothesized that HP milk supplementation to LBW pups during early postnatal life would impact hypothalamic appetite neuronal pathways development with consequences, at adulthood, on energy homeostasis regulation. Rat pups born with a LBW were equipped with gastrostomy tubes on the fifth day of life. They received a milk formula with either normal protein (NP, 8.7 g protein/dl) or high protein content (HP; 13.0 g protein/dl) and were subsequently weaned to a standard, solid diet at postnatal day 21. Rats that had been fed HP content milk gained more weight at adulthood associated with an increase of plasma insulin, leptin and triglycerides concentrations compared to NP rats. Screening performed on hypothalamus in development from the two groups of rats identified higher gene expression for cell proliferation and neurotrophin markers in HP rats. Despite these molecular differences, appetite neuronal projections emanating from the arcuate nucleus did not differ between the groups. Concerning feeding behavior at adulthood, rats that had been fed HP or NP milk exhibited differences in the satiety period, resting postprandial duration and nocturnal meal pattern. The consequences of HP milk supplementation after LBW will be discussed in regard to neural development and metabolic anomalies.     

The COVID-19 pandemic and birth outcomes in 2020: The role of prenatal care and other channels

We use national birth data to assess the associations between the COVID-19 pandemic during 2020 and birth outcomes in Uruguay. Employing interrupted time series difference-in-differences techniques, we find mixed results, with some pregnancies showing increases in the likelihood of very preterm or very-low-weight births, and some others showing decreases in the incidence of moderate prematurity and moderate low birth weight. Adverse outcomes are more likely among women with low education, women with previous children, and with risk factors, such as smoking or being older than 34. We observe improvements in health at birth for children of non-smokers, women younger than 35, and women with no other children. We underscore the role of health care by showing that women in the private sector, who suffered the strongest contraction in face-to-face prenatal care use, experienced more adverse birth outcomes. Our results also suggest that the economic recession and an increased burden of childcare were behind the increases in preterm and very-low-weight births. Because pollution is an unlikely channel for the positive results, we hypothesize that for some pregnancies, the pandemic improved the intrauterine habitat by leading to a quieter and healthier lifestyle.     

The role and interaction of imprinted genes in human fetal growth

Identifying the genetic input for fetal growth will help to understand common, serious complications of pregnancy such as fetal growth restriction. Genomic imprinting is an epigenetic process that silences one parental allele, resulting in monoallelic expression. Imprinted genes are important in mammalian fetal growth and development. Evidence has emerged showing that genes that are paternally expressed promote fetal growth, whereas maternally expressed genes suppress growth. We have assessed whether the expression levels of key imprinted genes correlate with fetal growth parameters during pregnancy, either early in gestation, using chorionic villus samples (CVS), or in term placenta. We have found that the expression of paternally expressing insulin-like growth factor 2 (IGF2), its receptor IGF2R, and the IGF2/IGF1R ratio in CVS tissues significantly correlate with crown–rump length and birthweight, whereas term placenta expression shows no correlation. For the maternally expressing pleckstrin homology-like domain family A, member 2 (PHLDA2), there is no correlation early in pregnancy in CVS but a highly significant negative relationship in term placenta. Analysis of the control of imprinted expression of PHLDA2 gave rise to a maternally and compounded grand-maternally controlled genetic effect with a birthweight increase of 93/155 g, respectively, when one copy of the PHLDA2 promoter variant is inherited. Expression of the growth factor receptor-bound protein 10 (GRB10) in term placenta is significantly negatively correlated with head circumference. Analysis of the paternally expressing delta-like 1 homologue (DLK1) shows that the paternal transmission of type 1 diabetes protective G allele of rs941576 single nucleotide polymorphism (SNP) results in significantly reduced birth weight (−132 g). In conclusion, we have found that the expression of key imprinted genes show a strong correlation with fetal growth and that for both genetic and genomics data analyses, it is important not to overlook parent-of-origin effects.     

极低出生体重婴幼儿发生宫外生长迟缓的危险性分析

目的:比较不同出生体重婴幼儿的生长特点,并分析影响极低出生体重婴幼儿发生宫外生长迟缓的危险因素。方法:回顾性调查2012年至2015年我院婴幼儿的临床资料,并按出生体重分成极低出生体重组和对照组,比较不同组别婴幼儿的差异性并采用logistics回归分析极低出生体重婴幼儿发生宫外生长迟缓的危险因素。结果:本次研究共收集婴幼儿200例,其中极低出生体重组118例,对照组82例,两组婴幼儿在胎龄、是否存在FGR或EUGR、首次接受肠内营养的时间、住院天数和出院时体重增长量上存在统计学差异,表现为极低出生体重组的婴幼儿的胎龄要小于对照组婴幼儿,且住院天数、首次接受肠内营养的时间和出院时体重增长量都要明显高于对照组婴幼儿,但对照组发生宫外生长迟缓和宫内生长受限的比例却明显低于极低出生体重组(P0.05)。针对极低出生体重婴幼儿的logistics回归分析显示,极低出生体重婴幼儿出生时伴有宫内生长受限或胎龄越小,则越有可能发生宫外生长迟缓(P0.05)。结论:极低出生体重的婴幼儿发生宫外生长迟缓的比例要明显高于低出生体重婴幼儿,其中婴幼儿本身的宫内生长受限和胎龄是影响极低出生体重婴幼儿发生宫外生长迟缓的最主要危险因素。     

Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat

Background

Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.

Methods

An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.

Results

Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.

Conclusions

These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.     

Fetal growth and neurobehavioral outcomes in childhood

Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood.     

Early development and reproductive lifespan of rabbit females: implications of growth rate,rearing diet and body condition at first mating

Factors influencing early development such as birth weight, nest competition, and the diet received during rearing have been proposed as elements conditioning the future reproductive performance of European rabbit (Oryctolagus cuniculus) females. To evaluate their effects, we followed the life of 1513 females from birth to time of death, culling or censoring (animals alive at a fixed date). Between 0 and 63 days of age 353 females died. From the remaining 1160 females, 864 were chosen based on their birth weight to be transferred from the selection to the production farm. At this farm, 431 females received the control diet (184 g of CP, 381 g of NDF and 11.8 MJ of DE per kg DM), while the other 433 received the fibrous diet (134 g of CP, 436 g of NDF and 10.0 MJ of DE per kg DM). Throughout the rearing period, we checked for the individual live weight and body condition (perirenal fat thickness) at first artificial insemination. Reproductive lifespan was defined as the number of days between the first parturition and the time of death, culling or censoring. Birth weight affected the survival of newborn females during lactation and the presence of a milk spot at birth (related to nest competition) increased the survivability of newborns weighing <45 g (P<0.001). Rearing diet altered the growth curve of females and their body condition at first insemination. The diet also altered the relative risk of death during the rearing period, which was lower among females fed on the fibrous diet (−12.5%; P<0.001). Therefore, a higher number of females fed with this diet reached their reproductive life, directly affecting the productivity measured per housed female. Fatter females at first insemination had smaller litter sizes and a higher risk of being culled than lean ones (P<0.05). In general, the fibrous diet reduced the risk of leaving the herd at early rearing, and both birth weight and perirenal fat thickness affected female’s reproductive lifespan. An excess of fat (positive change in one unit of perirenal fat) at their first insemination represented an increased the risk of death or elimination of 13%.     

Physical growth of children under five years of age in Nchelenge,Zambia: Results from a district survey

This study focuses on the physical growth of children aged 0–60 months in Nchelenge District, northeast Zambia. By means of a two-stage clustered and random sampling method, 193 households were selected. Weight, height, and mid-upper-arm circumference (MUAC) of children 0–60 months were measured. Underweight, stunting, and wasting were defined as weight for age, height for age, and weight for height (W/H), respectively, ≤2 z scores below the median of the National Center for Health Statistics (NCHS) reference population. Among 250 children, prevalence rates of 30% underweight, 69.2% stunting, and 4.4% wasting were found, with the highest rates at age 12–<24 months. Prevalence of stunting, underweight, and wasting in children aged 0–<6 months and 6–<12 months suggested that a substantial proportion of infants were premature and/or small for gestational age. The literature suggests that prematurity and intrauterine growth retardation may be quite common in Africa, and this may have important implications for the interpretation of growth data and under nutrition rates. Use of the MUAC < 125 mm as an indicator of wasting resulted in higher estimates of wasting compared to W/H ≤ −2 z scores, and seemed unsuitable as a screening test for wasting in this Zambian population. © 1996 Wiley-Liss, Inc.     

Maternal age and parity influence ultrasonographic measurements of fetal growth in Dutch Warmblood mares

Ultrasonographic examination of the equine fetus in mid-late gestation is usually performed only if there are concerns about fetal or maternal health. Even then it is difficult to determine whether development is ‘normal’ for gestational age because the reference values include considerable error margins. This study examined maternal factors that influence fetal growth with the aim of producing more precise late gestation fetal growth curves for Dutch Warmblood horses. Fetal development was monitored at 2-week intervals from day 100 of gestation until term in 32 mares ranging from 4 to 18 years in age; seven of the mares were primiparous. Transrectal and/or transabdominal ultrasonographic measurement of the fetal eye orbit, cranium, aorta, heart rate and of the combined thickness of uterus and placenta (CTUP) were performed using a portable ultrasound machine equipped with 6 MHz linear and 3.5 MHz curved array probes.During days 100–250 of gestation, the CTUP was thicker in primiparous than multiparous mares (p < 0.05). After day 220 the maximum cross-sectional area, but not diameter, of both the eye orbit and cranium were also greater in primiparous than multiparous mares (p < 0.05). Fetal aorta diameter was not influenced by parity but was affected by maternal age, being smaller in mares ≥15 years of age than younger animals (p < 0.05). Only biparietal cross-sectional surface area and aorta diameter increased linearly throughout late gestation. However, even allowing for the effects of parity and maternal age, the late gestational variation in fetal size is such that serial measurements may be required to definitively identify abnormal development.     

Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR

Background

Accumulating evidence reveals that intrauterine growth retardation (IUGR) can cause varying degrees of pulmonary arterial hypertension (PAH) later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR.

Methods

The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC) were isolated from the rat lungs by magnetic-activated cell sorting (MACS). We investigated epigenetic regulation of the endothelin-1 (ET-1) gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia.

Results

The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α) binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling.

Conclusions

These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.     

Inhibition of placental ornithine decarboxylase by DL-alpha-difluoro-methyl ornithine causes fetal growth restriction in rat

The roles of polyamines in intrauterine growth restriction (IUGR) is studied. The DL-alpha-difluoromethyl ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) which is a rate limiting enzyme of polyamine synthesis was administrated to pregnant rats so that we obtained rat fetuses with IUGR. The changes of maternal nutrition, damage of the placenta, and the direct effect of DFMO on the fetus were examined in this IUGR model. Administration of DFMO did not induced changes of maternal nutrition except for triglyceride and the fetal metabolic state. But the placental weight, ODC activity, and DNA in the placenta were decreased significantly. The ODC activity in the total placenta decreased to less than 10% of that of the control. Depression of ODC activity in the placenta may be the major cause of IUGR induced by DFMO administration, and polyamines play important roles to carry pregnancy.     

Consequences of a low litter birth weight phenotype for postnatal lean growth performance and neonatal testicular morphology in the pig

The consequences of a low litter average birth weight phenotype for postnatal growth performance and carcass quality of all progeny, and testicular development in male offspring, were investigated. Using data from 25 sows with one, and 223 sows with two consecutive farrowing events, individual birth weight (BW) was measured and each litter between 9 and 16 total pigs born was classified as low (LBW), medium (MBW) or high (HBW) birth weight: low and high BW being defined as >1 standard deviation below or above, respectively, the population mean for each litter size. Litter average BW was repeatable within sows. At castration, testicular tissue was collected from 40 male pigs in LBW and HBW litters with individual BW close to their litter average BW and used for histomorphometric analysis. LBW piglets had a lower absolute number of germ cells, Sertoli cells and Leydig cells in their testes and a higher brain : testis weight ratio than HBW piglets. Overall, LBW litters had lower placental weight and higher brain : liver, brain : intestine and brain : Semitendinosus muscle weight ratios than MBW and HBW litters. In the nursery and grow–finish (GF) phase, pigs were kept in pens by BW classification (9 HBW, 17 MBW and 10 LBW pens) with 13 males and 13 females per pen. Average daily gain tended to be lower in LBW than HBW litters in lactation (P = 0.06) and throughout the nursery and GF phases (P < 0.01), resulting in an increasing difference in body weight between LBW, MBW and HBW litters (P < 0.05). Average daily feed intake was lower (P < 0.001) in LBW than HBW litters in the nursery and GF phases. Feed utilization efficiency (feed/gain) was similar for LBW and HBW litters in the nursery, but was lower (P < 0.001) in HBW than LBW litters in the GF phase. By design, slaughter weight was similar between BW classifications; however, LBW litters needed 9 more days to reach the same slaughter weight than HBW litters (P < 0.001). BW classification did not affect carcass composition traits. In conclusion, LBW litters showed benchmarks of intrauterine growth retardation, LBW had a negative impact on testicular development and germ and somatic cell populations, and was associated with decreased postnatal growth during all phases of production; however, no measurable effect on carcass composition traits was established.     

Compensatory growth feeding strategy does not overcome negative effects on growth and carcass composition of low birth weight pigs

The aim of this study was to evaluate whether the compensatory growth feeding strategy could be a suitable solution for overcoming the negative effects on growth, carcass composition and meat quality of low birth weight pigs. Forty-two Swiss Large White barrows from 21 litters were selected at weaning and categorized into either being light (L; >0.8 and <1.3 kg) or heavy (H; >1.7 kg) birth weight pigs. From 27.8 kg BW, pigs were assigned within birth weight group to one of three feeding groups: AA: ad libitum access to the grower and finisher diet, RR: restricted access to the grower and finisher diet or RA: restricted access to the grower diet and ad libitum access to the finisher diet. At slaughter, the longissimus (LM) and semitendinosus (STM) muscles were removed from the right side of the carcass. Weight, girth and length of the STM and the LM area were determined after muscle excision. Carcass characteristics and meat quality traits were assessed. Using mATPase histochemistry, myofibre size and myofibre type distribution were determined in the LM and STM. Because of longer days on feed, total feed intake was greater (P<0.01) and feed efficiency was lower (P<0.01) in L than H barrows. Regardless of the birth weight group, AA and RA barrows grew faster (P<0.05) than RR barrows. During the compensatory growth period, RA barrows grew faster (P<0.05) than AA or RR barrows. Growth efficiency did not differ between RA and RR barrows but was greater (P<0.05) compared with AA barrows. Carcasses of L barrows were fatter as indicated by the lower (P⩽≤0.05) lean meat and greater (P⩽0.02) omental and subcutaneous fat percentage. Lean meat percentage was lower (P⩽0.05) in AA and RA than RR barrows. These differences caused by ad libitum feed access tended to be greater (feeding regime × birth weight group interaction; P<0.08) in L than H barrows. In L barrows, slow oxidative, fast oxidative glycolytic and overall average myofibre size of the LM and the fast glycolytic myofibres and overall average myofibre size of the dark portion of the STM were larger (P⩽0.03) than in H barrows. The study revealed that the compensatory growth feeding strategy was inadequate in overcoming the disadvantages of low birth weight.     

The biomarkers of fetal growth in intrauterine growth retardation and large for gestational age cases: from adipocytokines to a metabolomic all-in-one tool

Adipose tissue is no longer considered as inert; the literature describes the role it plays in the production of many substances, such as adiponectin, visfatin, ghrelin, S100B, apelin, TNF, IL-6 and leptin. These molecules have specific roles in humans and their potential as biomarkers useful for identifying alterations related to intrauterine growth retardation and large for gestational age neonates is emerging. Infants born in such conditions have undergone metabolic changes, such as fetal hypo- or hyperinsulinemia, which may lead to development of dysmetabolic syndrome and other chronic diseases in adulthood. In this review, these biomarkers are analyzed specifically and it is discussed how metabolomics may be an advantageous tool for detection, discrimination and prediction of metabolic alterations and diseases. Thus, a holistic approach, such as metabolomics, could help the prevention and early diagnosis of metabolic syndrome.     

Intrauterine Growth Retardation (Malnutrition by Vascular Ligation) Induces Modifications in Fatty Acid Composition of Neurons and Oligodendrocytes

Intrauterine growth retardation (IUGR) induced by ligation of one uterine artery on day 17 of pregnancy in the rat lead to major abnormalities in the fatty acid content of neurons and oligodendrocytes but not in astrocytes. In neurons from IUGR rats, monounsaturated fatty acids were decreased; in the polyunsaturated series, ω-3 fatty acids were increased and Ω-6 fatty acids were decreased. In oligodendrocytes, monounsaturated fatty acids were also decreased, but the modifications in polyunsaturated fatty acids were the opposite of those in neurons: Ω-3 being decreased and w-6 increased. Although the animals received a normal diet after birth, the alterations were still present in adulthood. In addition, fatty acid composition of brain cells is a very indicative criterion of brain maturation.     

Prenatal care demand and its effects on birth outcomes by birth defect status in Argentina

Our objective was to identify determinants of prenatal care demand and evaluate the effects of this demand on low birth weight and preterm birth. Delay in initiating prenatal care was modeled as a function of pregnancy risk indicators, enabling factors, and regional characteristics. Conditional maximum likelihood (CML) estimation was used to model self-selection into prenatal care use when estimating its effectiveness. Birth registry data was collected post delivery on infants with and without common birth defects born in 1995-2002 in Argentina using a standard procedure. Several maternal health and fertility indicators had significant effects on prenatal care use. In the group without birth defects, prenatal care delay increased significantly LBW and preterm birth when accounting for self-selection using the CML model but not in the standard probit model. Prenatal care was found to be ineffective on average in the birth defect group. The self-selection of higher risk women into earlier initiation of prenatal care resulted in underestimation of prenatal care effectiveness when using a standard probit model with several covariates. Large improvements in birth outcomes are suggested with earlier initiation of prenatal care for pregnancies uncomplicated with birth defects in Argentina, implying large opportunity costs from the long waiting time observed in this sample (about 17 weeks on average). The suggested ineffectiveness for pregnancies complicated with common birth defects deserves further research.