Differences In Fetal Growth Research Articles

Prenatal exposure to dexamethasone in the mouse induces sex-specific differences in placental gene expression.

Prenatal stress during pregnancy leads to sex-specific effects on fetal development and disease susceptibility over the life span; however, the origin of sex differences has not been identified. The placenta not only plays a key role in fetal growth and development throughout pregnancy, but also affects the fetal programming underlying subsequent adult health and accounts. Therefore, sex-specific adaptation of the placenta may be central to the sex differences in fetal growth and survival. Here, we analyzed the effects of prenatal dexamethasone (Dex) on sex-specific changes in placental gene expression using RNA-Seq. Placental tissues from males and females were separated into two developmentally distinct fetal and maternal parts at E11.5 stage. The majority of genes in female placentas were downregulated by prenatal Dex, whereas those were mostly maintained or rather upregulated in male placentas. RNA-Seq results were validated using independent biological replicates from the same stage and placental tissue samples from E18.5 by realtime PCR assays. Activation of various inflammatory response-related genes, chemokines and their receptors, particularly in male placentas, strongly implies that prenatal Dex exposure causes sex-specific physiological responses that can lead to inflammatorydiseases involving vascularpathology.

Parental Characteristics can Explain Why Japanese Women Give Birth to the Smallest Infants in the United States.

Whether birthweight differences observed between races are due to modifiable factors remains controversial. In the United States, Asian infants weigh less than white infants and Japanese infants weigh the least. Using US Natality data, we evaluated 4132319 singleton term livebirths to parents of non-Hispanic white or Japanese race/ethnicity from 2009 to 2012. Infants were categorised by parental race/ethnicity (both white, n=4116637; Japanese father/white mother, n=2377; white father/Japanese mother, n=7478; both Japanese, n=5827). We used multivariable regression to sequentially adjust for maternal characteristics to determine to what extent they explained differences in fetal growth due to maternal race/ethnicity. Infants born to Japanese mothers were smaller by 132 (95% CI 101, 122) grams, with higher risk of small for gestational age (relative risk ratio (RRR) 1.56 (95% CI 1.47, 1.65) and lower risk of large for gestational age RRR 0.49, 95% CI 0.44, 0.54), compared to infants of white mothers. Differences in social factors and in maternal age, parity, and gestational age only minimally explained this difference. However, additionally adjusting for maternal height, body mass index and gestational weight gain substantially attenuated this difference to 20 (95% CI 12, 29) grams in birthweight, 0.91 (95% CI 0.86, 0.97) times risk of small for gestational age, and 1.06 (95% CI 0.96, 1.17) times risk of large for gestational age, with the effect similar across strata of paternal race/ethnicity. Differences in fetal growth between infants from Japanese and white mothers could be explained by differences in maternal height, pre-pregnancy weight, and gestational weight gain. Fetal growth potential appears to be similar across racial/ethnic groups when parental sizes are similar.

Males are from Mars, and females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity

Maternal obesity is associated with adverse neurodevelopmental outcomes in children, including autism spectrum disorders, developmental delay, and attention-deficit hyperactivity disorder. The underlying mechanisms remain unclear. We previously identified second-trimester amniotic fluid and term cord blood gene expression patterns suggesting dysregulated brain development in fetuses of obese compared with lean women. We sought to investigate the biological significance of these findings in a mouse model of maternal diet-induced obesity. We evaluated sex-specific differences in fetal growth, brain gene expression signatures, and associated pathways. Female C57BL/6J mice were fed a 60% high-fat diet or 10% fat control diet for 12-14 weeks prior to mating. During pregnancy, obese dams continued on the high-fat diet or transitioned to the control diet. Lean dams stayed on the control diet. On embryonic day 17.5, embryos were weighed and fetal brains were snap frozen. RNA was extracted from male and female forebrains (10 per diet group per sex) and hybridized to whole-genome expression arrays. Significantly differentially expressed genes were identified using a Welch's t test withthe Benjamini-Hochberg correction. Functional analyses were performed using ingenuity pathways analysis and gene set enrichment analysis. Embryos of dams on the high-fat diet were significantly smaller than controls, with males more severely affected than females (P= .01). Maternal obesity and maternal obesity with dietary change in pregnancy resulted in significantly more dysregulated genes in male vs female fetal brains (386 vs 66, P < .001). Maternal obesity with and without dietary change in pregnancy was associated with unique brain gene expression signatures for each sex, with an overlap of only 1 gene. Changing obese dams to a control diet in pregnancy resulted in more differentially expressed genes in the fetal brain than maternal obesity alone. Functional analyses identified common dysregulated pathways in both sexes, but maternal obesity and maternal dietary change affected different aspects of brain development in males compared with females. Maternal obesity is associated with sex-specific differences in fetal size and fetal brain gene expression signatures. Male fetal growth and brain gene expression may be more sensitive toenvironmental influences during pregnancy. Maternal diet during pregnancy has a significant impact on the embryonic brain transcriptome. It is important toconsider both fetal sex and maternal diet when evaluating the effects ofmaternal obesity on fetal neurodevelopment.

Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies

Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were: humerus and femur lengths (10 weeks), abdominal circumference (16 weeks), head circumference (21 weeks), and biparietal diameter (27 weeks). The study-derived standard based solely on the white group erroneously classifies as much as 15% of non-white fetuses as growth restricted (EFW <5th percentile). Significant differences in fetal growth were found among the 4 groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth.

Sex-specific differences in fetal growth in newborns exposed prenatally to traffic-related air pollution in the PELAGIE mother–child cohort (Brittany, France)

BackgroundNumerous studies have linked prenatal traffic-related air pollution exposure to fetal growth. Recently, several studies have suggested exploring this association independently among boys and girls because of potential sex-specific biological vulnerability to air pollution. Residence-based factors can also influence fetal growth by enhancing susceptibility to the toxic effects of air pollution and must also be considered in these relations. ObjectiveWe examined sex-specific associations between prenatal air pollution exposure and fetal growth and explored whether they differed by the urban–rural status of maternal residence. MethodsThis study relied on the PELAGIE mother–child cohort (2521 women, Brittany, France, 2002–2006). Fetal growth was assessed through birth weight, head circumference and small weight (SGA) and small head circumference (SHC) for gestational age. Nitrogen dioxide (NO2) concentrations at mothers’ homes were estimated by using a land use regression model taking into account temporal variation during pregnancy. Associations between estimated NO2 concentrations and fetal growth were assessed with linear regression or logistic regression models, depending on the outcome investigated. ResultsAn interquartile range (8.8µgm−3) increase in NO2 exposure estimates was associated with a 27.4g (95% CI 0.8 to 55.6) increase in birth weight and a 0.09cm (95% CI 0.00–0.17) significant increase in head circumference, among newborn boys only. Their risks of SGA and SHC were reduced (OR 0.70, 95% CI 0.53–0.92, OR 0.76, 95% CI 0.56–1.03, respectively, for an increase of 8.8µgm−3). No statistically significant trends were observed among girls. Urban–rural status modified the effect of air pollution only for SHC and again only for newborn boys. ConclusionFindings from this study confirm the need to consider sex-specific associations between air pollution and fetal growth and to investigate possible mechanisms by which traffic-related air pollution may increase anthropometric parameters at birth.

Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on Placental Morphology, Function and Pregnancy Outcome

Vitamin D deficiency has been implicated in the pathogenesis of several pregnancy complications attributed to impaired or abnormal placental function, but there are few clues indicating the mechanistic role of vitamin D in their pathogenesis. To further understand the role of vitamin D receptor (VDR)-mediated activity in placental function, we used heterozygous Vdr ablated C57Bl6 mice to assess fetal growth, morphological parameters and global gene expression in Vdr null placentae. Twelve Vdr +/- dams were mated at 10–12 weeks of age with Vdr +/- males. At day 18.5 of the 19.5 day gestation in our colony, females were euthanised and placental and fetal samples were collected, weighed and subsequently genotyped as either Vdr +/+, Vdr +/- or Vdr -/-. Morphological assessment of placentae using immunohistochemistry was performed and RNA was extracted and subject to microarray analysis. This revealed 25 genes that were significantly differentially expressed between Vdr +/+ and Vdr -/- placentae. The greatest difference was a 6.47-fold change in expression of Cyp24a1 which was significantly lower in the Vdr -/- placentae (P<0.01). Other differentially expressed genes in Vdr -/- placentae included those involved in RNA modification (Snord123), autophagy (Atg4b), cytoskeletal modification (Shroom4), cell signalling (Plscr1, Pex5) and mammalian target of rapamycin (mTOR) signalling (Deptor and Prr5). Interrogation of the upstream sequence of differentially expressed genes identified that many contain putative vitamin D receptor elements (VDREs). Despite the gene expression differences, this did not contribute to any differences in overall placental morphology, nor was function affected as there was no difference in fetal growth as determined by fetal weight near term. Given our dams still expressed a functional VDR gene, our results suggest that cross-talk between the maternal decidua and the placenta, as well as maternal vitamin D status, may be more important in determining pregnancy outcome than conceptus expression of VDR.

Non-Genetic Inheritance, Fertility and Assisted Reproductive Technologies

AbstractThe concept of non-genetic inheritance is gaining considerable attention in the assisted reproductive technology (ART) community due to the reported differences between children born from ART and those that are conceived naturally. It has been demonstrated that children conceived via ART have differences in fetal growth, birth weight, congenital abnormalities, cardiometabolic parameters, glucose homeostasis as well as changes to body composition compared to children conceived naturally. Although these changes may have a parental contribution and may be influenced by the pathology of infertility there is concern that the technologies themselves may play a role. In support of this, is emerging evidence that aspects of ART technology such as culture media formulation and insemination method can alter offspring phenotype. In addition it is also documented that exposure to environmental factors, such as toxins can impact on offspring gametogenesis such that these perturbations persist through generations. With the increasing use of ART and the development of new technologies it is vital that we understand whether ART can effect non-genetic inheritance so that we can optimise technology and prevent abnormal programming and its impact on all aspects of offspring health including fertility and a possible transmission to subsequent generations.

The influence of weight gain patterns in pregnancy on fetal growth using cluster analysis in an obese and nonobese population

Excessive weight gain during pregnancy has an important influence on fetal growth and on weight development in future generations. A prospective cohort study of 325 obese and nonobese Caucasian women with naturally conceived, singleton pregnancies was performed. They were followed up until delivery for maternal weight gain and for fetal growth with ultrasound-based weight estimations and final birth weight. Using cluster analysis distinct profiles of maternal weight gain during pregnancy were obtained. Longitudinal regression analysis was performed to investigate the relationship of the maternal weight gain profile and BMI on fetal growth and final birth weight. Cluster analysis revealed four discernable maternal weight gain profiles: 12 cases (3.7%) ended up at their starting weight or decreased in weight (cluster 1), 16 cases (4.9%) who slightly increased in weight (maximum 4 kg) as compared to their initial weight (cluster 2), 114 cases (35.1%) who gained between 4 and 12 kg in weight (cluster 3), and 183 cases (56.3%) who showed the largest weight gain: more than 12 kg (cluster 4). There were statistically significant differences in fetal growth associated with weight gain cluster, which became apparent late in the second trimester and increased toward the end of pregnancy. Maternal BMI and maternal weight gain profile were independent predictors of fetal growth and birth weight. Therefore, the conclusion is that the cluster analysis permits to discern four gestational weight gain (GWG) patterns in obese and nonobese subjects and that both maternal BMI and maternal weight gain pattern during pregnancy positively influence fetal growth and birth weight.

PP076. Gender differences in fetal growth and fetal-placental ratio in preeclamptic and normal pregnancies

Boys have higher morbidity and mortality than girls,particularly when born prematurely, despite higher birthweight. Adaptation to poor intrauterine environment by reducing fetal growth is more prevalent in female than male fetuses. Differences in reponses between the genders might be mediated by placental functions, as illustrated by the fetal-placental ratio. To study the fetal-placental ratio in normal and preeclamptic pregnancies and compare this ratio in boys and girls. The STORK study (n=1031) is a prospective, longitudinal study of fetal growth. We calculated fetal-placental ratio for boys and girls in normal and preeclamptic pregnancies. Differences between groups were analysed by independent t-tests. Boys had a higher fetal-placental ratio than girls (5.26 vs 5.1 g, p=0.015) in normal pregnancies. 39 women (3.8%) developed preeclampsia. Boys had the same ratio in both groups. Girls in preeclamptic pregnancies had a lower ratio than in normal pregnancies (4.5 vs 5.1 g, p=0.05). Boys appear to invest more in their own growth than in placental growth. In preeclampsia they maintain the same fetal-placental ratio. In girls, birthweight is lower whereas placental weight is maintained, giving a reduced fetal-placental ratio. This pattern is more pronounced in preeclampsia. #Birthweight according to gestational age * corrected for gestational age.

Maternal snoring during pregnancy is not associated with fetal growth restriction

A small number of studies have, thus far, evaluated the association between maternal snoring and fetal growth revealing conflicting results. No study has compared fetal growth between women with habitual snoring who snored before pregnancy and women with habitual snoring that started to snore during pregnancy.Objectives: To examine the effect of maternal snoring on fetal outcome and to investigate the differences between “chronic snorers” and “new-onset snorers”. Methods: Women of singleton, uncomplicated, full-term pregnancies completed a questionnaire. Obstetric and labor records were reviewed. Newborn records were reviewed for gestational age, birth weight, Apgar score and gender. Results: 246 low risk women were studied. Mean BMI at the beginning of pregnancy was 22.3 ± 3.5 kg/m2. 32% reported habitual snoring. Of those, 26% were chronic snorers and 74% were new-onset snorers. Neither significant difference in fetal growth was found between snorers and non-snorers nor between chronic snorers and new-onset snorers. Increased rate of nulliparous women was found in new-onset snorers compared with both chronic snorers and non-snorers (54 vs. 25 and 29% respectively; p = 0.001). Conclusions: In pregnant women with no apparent risk factors, maternal snoring does not affect fetal growth. No differences in maternal characteristics or fetal outcome were found between chronic snorers and new-onset snorers.

Challenges in defining and classifying the preterm birth syndrome

In 2009, the Global Alliance to Prevent Prematurity and Stillbirth Conference charged the authors to propose a new comprehensive, consistent, and uniform classification system for preterm birth. This first article reviews issues related to measurement of gestational age, clinical vs etiologic phenotypes, inclusion vs exclusion of multifetal and stillborn infants, and separation vs combination of pathways to preterm birth. The second article proposes answers to the questions raised here, and the third demonstrates how the proposed system might work in practice.

Sex-specific differences in placental global gene expression in pregnancies complicated by asthma

BackgroundChronic maternal asthma is associated with reduced growth of the female fetus and normal growth of the male fetus. The mechanisms that control the differential effects of maternal asthma on the fetus have not been fully elucidated but alterations in placental function may play a role. In the current study we have used microarray platform to examine fetal sex-specific global changes in placental gene expression in pregnancies complicated by asthma as compared to non-asthmatic subjects. MethodsPlacental RNA was extracted from 11 control subjects and 38 asthmatic subjects. Labeled cDNA was hybridized to an oligonucleotide chip with 1700 double spotted well-characterized human genes. Global gene expression data analysis and visualization were performed using the Binary Tree-Structured Vector Quantization (BTSVQ) software. Functional relationships of differentially expressed genes were assessed using protein–protein interaction database I2D, network analysis and visualization software NAViGaTOR and Ingenuity Pathway Analysis software. ResultsOverall, 65 genes were found to be altered in placentae of pregnancies complicated by asthma. Of these, only 6 genes were altered in male placentae. There were 59 gene changes in female placentae of asthmatic mothers relative to control placentae. Some of the sex-specific genes were associated with growth, inflammation and immune pathways. ConclusionThere are sex-specific alterations in placental gene expression in the presence of maternal asthma. Given that many of the identified genes in the female placentae were associated with or involved in cellular growth and tissue development, these may contribute to the sexually dimorphic difference in fetal growth in response to maternal asthma.

Review: Sex and the Human Placenta: Mediating Differential Strategies of Fetal Growth and Survival

There are known sex specific differences in fetal and neonatal morbidity and mortality. There are also known differences in birthweight centile with males generally being larger than females at birth. These differences are generally ignored when studying obstetric complications of pregnancy and the mechanisms that confer these differences between the sexes are unknown. Current evidence suggests sex specific adaptation of the placenta may be central to the differences in fetal growth and survival. Our research examining pregnancies complicated by asthma has reported sexually dimorphic differences in fetal growth and survival with males adapting placental function to allow for continued growth in an adverse maternal environment while females reduce growth in an attempt to survive further maternal insults. We have reported sex differences in placental cytokine expression, insulin-like growth factor pathways and the placental response to cortisol in relation to the complication of asthma during pregnancy. More recently we have identified sex specific alterations in placental function in pregnancies complicated by preterm delivery which were associated with neonatal outcome and survival. We propose the sexually dimorphic differences in growth and survival of the fetus are mediated by the sex specific function of the human placenta. This review will present evidence supporting this hypothesis and will argue that to ignore the sex of the placenta is no longer sound scientific practice.

Sex differences in fetal growth responses to maternal height and weight

Sex differences in fetal growth have been reported, but how this happens remains to be described. It is unknown if fetal growth rates, a reflection of genetic and environmental factors, express sexually dimorphic sensitivity to the mother herself. This analysis investigated homogeneity of male and female growth responses to maternal height and weight. The study sample included 3,495 uncomplicated singleton pregnancies followed longitudinally. Analytic models regressed fetal and neonatal weight on tertiles of maternal height and weight, and modification by sex was investigated (n = 1,814 males, n = 1,681 females) with birth gestational age, maternal parity, and smoking as covariates. Sex modified the effects of maternal height and weight on fetal growth rates and birth weight. Among boys, tallest maternal height influenced fetal weight growth before 18 gestational weeks of age (P = 0.006), and prepregnancy maternal weight and body mass index subsequently had influence (P < 0.001); this was not found among girls. Additionally, interaction terms between sex, maternal height, and maternal weight identified that males were more sensitive to maternal weight among shorter mothers (P = 0.003) and more responsive to maternal height among lighter mothers (P < or = 0.03), compared to females. Likewise, neonatal birth weight dimorphism varied by maternal phenotype. A male advantage of 60 g occurred among neonates of the shortest and lightest mothers (P = 0.08), compared to 150 and 191 g among short and heavy mothers, and tall and light-weight mothers, respectively (P = 0.01). Sex differences in response to maternal size are under-appreciated sources of variation in fetal growth studies and may reflect differential growth strategies.

Gender differences in fetal growth of newborns exposed prenatally to airborne fine particulate matter

Our primary purpose was to assess sex-specific fetal growth reduction in newborns exposed prenatally to fine particulate matter. Only women 18–35 years of age, who claimed to be non-smokers, with singleton pregnancies, without illicit drug use and HIV infection, free from chronic diseases were eligible for the study. A total of 481 enrolled pregnant women who gave birth between 37 and 43 weeks of gestation were included in the study. Prenatal personal exposure to fine particles over 48h during the second trimester was measured using personal monitors. To evaluate the relationship between the level of PM2.5 measured over 48h in the second trimester of pregnancy with those in the first and the third trimesters, a series of repeated measurements in each trimester was carried out in a random subsample of 85 pregnant women. We assessed the effect of PM2.5 exposure on the birth outcomes (weight, length and head circumference at birth) by multivariable regression models, controlling for potential confounders (maternal education, gestational age, parity, maternal height and prepregnancy weight, sex of infant, prenatal environmental tobacco smoke, and season of birth). Birth outcomes were associated positively with gestational age, parity, maternal height and prepregnancy weight, but negatively with the level of prenatal PM2.5 exposure. Overall average increase in gestational period of prenatal exposure to fine particles by about 30μg/m3, i.e., from 25th percentile (23.4μg/m3) to 75th percentile (53.1μg/m3) brought about an average birth weight deficit of 97.2g (95% CI: −201, 6.6) and length at birth of 0.7cm (95% CI: −1.36, −0.04). The corresponding exposure lead to birth weight deficit in male newborns of 189g (95% CI: −34.2, −343) in comparison to 17g in female newborns; the deficit of length at birth in male infants amounted to 1.1cm (95% CI: −0.11, −2.04). We found a significant interrelationship between self-reported ETS and PM2.5, however, none of the models showed a significant interaction of both variables. The joint effect of various levels of PM2.5 and ETS on birth outcomes showed the significant deficit only for the categories of exposure with higher component of PM2.5. Concluding, the results of the study suggest that observed deficits in birth outcomes are rather attributable to prenatal PM2.5 exposure and not to environmental tobacco smoke. The study also provided evidence that male fetuses are more sensitive to prenatal PM2.5 exposure and this should persuade policy makers to consider birth outcomes by gender separately while setting air pollution guidelines.

Fetal Growth Among Infants With Congenital Heart Defects by Maternal Race/Ethnicity

Congenital heart defects (CHDs) are the most prevalent birth defects. Infants with CHDs more often are small-for-gestational age (SGA) than infants without CHD; however, little is known about racial/ethnic variations in prevalence of SGA or large-for-gestational age (LGA) for infants born with CHDs. This study determined the risk of SGA and LGA for non-Hispanic (NH)-black and Hispanic infants with CHDs. Data from the Florida Birth Defects Registry were used in a retrospective cohort study of 10,027 live-born infants to resident NH-White, NH-Black, and Hispanic women ages 15-49 years from January 1, 1998, to December 31, 2003, and diagnosed with 11 CHDs. Defect-specific odds ratios and 95% confidence intervals were computed for risk of SGA and LGA by race/ethnicity and adjusted for covariates using multinomial logistic regression. After adjusting for covariates, we found there were no statistically significant racial/ethnic differences in risk of SGA. However, NH-Blacks with ventricular septal defect had increased risk of LGA and NH-Blacks with tetralogy of Fallot had decreased risk of LGA compared to NH-Whites. Very few racial/ethnic differences in fetal growth are present among infants with CHD. Further elucidation of the factors involved in fetal growth and the impact of CHD itself on fetal development is needed.

Where the O2goes to: preservation of human fetal oxygen delivery and consumption at high altitude

Fetal growth is decreased at high altitude (> 2700 m). We hypothesized that variation in fetal O(2) delivery might account for both the altitude effect and the relative preservation of fetal growth in multigenerational natives to high altitude. Participants were 168 women of European or Andean ancestry living at 3600 m or 400 m. Ancestry was genetically confirmed. Umbilical vein blood flow was measured using ultrasound and Doppler. Cord blood samples permitted calculation of fetal O(2) delivery and consumption. Andean fetuses had greater blood flow and oxygen delivery than Europeans and weighed more at birth, regardless of altitude (+208 g, P < 0.0001). Fetal blood flow was decreased at 3600 m (P < 0.0001); the decrement was similar in both ancestry groups. Altitude-associated decrease in birth weight was greater in Europeans (-417 g) than Andeans (-228 g, P < 0.005). Birth weight at 3600 m was > 200 g lower for Europeans at any given level of blood flow or O(2) delivery. Fetal haemoglobin concentration was increased, decreased, and the fetal / curve was left-shifted at 3600 m. Fetuses receiving less O(2) extracted more (r(2) = 0.35, P < 0.0001). These adaptations resulted in similar fetal O(2) delivery and consumption across all four groups. Increased umbilical venous O(2) delivery correlated with increased fetal O(2) consumption per kg weight (r(2) = 0.50, P < 0.0001). Blood flow (r(2) = 0.16, P < 0.001) and O(2) delivery (r(2) = 0.17, P < 0.001) correlated with birth weight at 3600 m, but not at 400 m (r(2) = 0.04, and 0.03, respectively). We concluded that the most pronounced difference at high altitude is reduced fetal blood flow, but fetal haematological adaptation and fetal capacity to increase O(2) extraction indicates that deficit in fetal oxygen delivery is unlikely to be causally associated with the altitude- and ancestry-related differences in fetal growth.

036. SEX SPECIFIC FUNCTION OF THE HUMAN PLACENTA: IMPLICATIONS FOR FETAL GROWTH AND SURVIVAL

The placenta plays a central role in the development of the fetus by modulating the supply of nutrients and oxygen throughout pregnancy. We have identified that the placenta adapts to the presence of a maternal pathophysiology in a sexually dimorphic manner which results in differences in fetal growth. We have reported that the female fetus reduces her growth in response to chronic maternal asthma which ensures her survival in the presence of an acute asthma exacerbation. Conversely the male fetus continues to grow normally in the presence of maternal asthma but this is associated with a poor outcome in the presence of an acute exacerbation. We propose that the sexually dimorphic response of the fetus is derived from differences in placental adaptation to a pathophysiological condition. In the presence of a female fetus and maternal asthma, we have observed global gene changes in the placenta accompanied by significant alterations in microRNA expression. Downstream of these alterations we have observed differences in protein expression especially in relation to placental cytokines and the glucocorticoid receptor. In the presence of a male fetus there are fewer changes in global placental gene and microRNA expression, and we have observed no alterations in expression of placental cytokines or the glucocorticoid receptor. These differential adaptations ensure increased survival of the female fetus and continued growth of the male fetus in adverse conditions.

Does one size fit all? The case for ethnic-specific standards of fetal growth

BackgroundBirth weight for gestational age is a widely-used proxy for fetal growth. Although the need for different standards for males and females is generally acknowledged, the physiologic vs pathologic nature of ethnic differences in fetal growth is hotly debated and remains unresolved.MethodsWe used all stillbirth, live birth, and deterministically linked infant deaths in British Columbia from 1981 to 2000 to examine fetal growth and perinatal mortality in Chinese (n = 40,092), South Asian (n = 38,670), First Nations, i.e., North American Indian (n = 56,097), and other (n = 731,109) births. We used a new analytic approach based on total fetuses at risk to compare the four ethnic groups in perinatal mortality, mean birth weight, and "revealed" (< 10th percentile) small-for-gestational age (SGA) among live births based on both a single standard and four ethnic-specific standards.ResultsDespite their lower mean birth weights and higher SGA rates (when based on a single standard), Chinese and South Asian infants had lower perinatal mortality risks throughout gestation. The opposite pattern was observed for First Nations births: higher mean birth weights, lower revealed SGA rates, and higher perinatal mortality risks. When SGA was based on ethnic-specific standards, however, the pattern was concordant with that observed for perinatal mortality.ConclusionThe concordance of perinatal mortality and SGA rates when based on ethnic-specific standards, and their discordance when based on a single standard, strongly suggests that the observed ethnic differences in fetal growth are physiologic, rather than pathologic, and make a strong case for ethnic-specific standards.

Spontaneously occurring differences in fetal weight do not affect blood pressure, the hypothalamic-pituitary-adrenal axis or the renin-angiotensin system in the late-gestation ovine fetus

Fetal growth restriction (FGR) has been associated with an increased incidence of cardiovascular disease in adult life. Animal models of restricted fetal growth often cause FGR over discrete periods of gestation and hence may not be applicable to individuals with low birthweight but who are not clinically growth-restricted. Our aim was to determine whether spontaneously occurring differences in fetal growth influence the functional development of the hypothalamic-pituitary-adrenal (HPA) axis or the renin-angiotensin system (RAS), both of which are involved in arterial pressure regulation. Using sheep, arterial pressure and heart rate were monitored in chronically catheterised singleton and twin fetuses at 130, 134 and 137 days of gestation (term approximately 147 days). Fetuses were challenged, at different times, with exogenous angiotensin (Ang) II, combined administration of arginine vasopressin and corticotrophin releasing hormone (AVP+CRH) and adrenocorticotrophic hormone (ACTH); fetal cardiovascular responses and circulating cortisol concentrations were measured. In all fetuses Ang II and AVP+CRH altered cardiovascular function (increase in mean arterial pressure and decrease in heart rate); both AVP+CRH and ACTH increased circulating cortisol concentrations. Responses were not related to fetal bodyweight. We conclude that naturally occurring differences in growth do not influence the development of the HPA axis or RAS function in fetal sheep.