Fetal Growth Trajectory Research Articles

BOARD INVITED REVIEW: Post-transfer consequences of in vitro-produced embryos in cattle.

In vitro embryo production (IVP) in cattle has gained worldwide interest in recent years, but the efficiency of using IVP embryos for calf production is far from optimal. This review will examine the pregnancy retention rates of IVP embryos and explore causes for pregnancy failures. Based on work completed over the past 25 yr, only 27% of cattle receiving IVP embryos will produce a live calf. Approximately 60% of these pregnancies fail during the first 6 wk of gestation. When compared with embryos generated by superovulation, pregnancy rates are 10% to 40% lower for cattle carrying IVP embryos, exemplifying that IVP embryos are consistently less competent than in vivo-generated embryos. Several abnormalities have been observed in the morphology of IVP conceptuses. After transfer, IVP embryos are less likely to undergo conceptus elongation, have reduced embryonic disk diameter, and have compromised yolk sac development. Marginal binucleate cell development, cotyledon development, and placental vascularization have also been documented, and these abnormalities are associated with altered fetal growth trajectories. Additionally, in vitro culture conditions increase the risk of large offspring syndrome. Further work is needed to decipher how the embryo culture environment alters post-transfer embryo development and survival. The risk of these neonatal disorders has been reduced by the use of serum-free synthetic oviductal fluid media formations and culture in low oxygen tension. However, alterations are still evident in IVP oocyte and embryo transcript abundances, timing of embryonic cleavage events and blastulation, incidence of aneuploidy, and embryonic methylation status. The inclusion of oviductal and uterine-derived embryokines in culture media is being examined as one way to improve the competency of IVP embryos. To conclude, the evidence presented herein clearly shows that bovine IVP systems still must be refined to make it an economical technology in cattle production systems. However, the current shortcomings do not negate its current value for certain embryo production needs and for investigating early embryonic development in cattle.

The effects of maternal nutrition around the time of conception on the health of the offspring

The incidence of prematurity, diabetes and cardiovascular disease have been increasing in both the developed and developing world. Increasing numbers of human studies suggest that these serious health outcomes may have developmental origins originating from nutritional deficits in the periconceptional period, with maternal nutrition around the time of conception now shown to have important effects on the length of gestation, trajectory of fetal growth and on postnatal growth and health. Biomedical research using the pregnant sheep has been widely employed to gain a deeper understanding of the underlying mechanisms involved. There is growing awareness that this field of research has major implications for the livestock production industry. From our own studies on sheep we have evidence that maternal undernutrition during the periconceptional period results in altered fetal hypothalamic-pituitary-adrenal axis (HPAA) development, an increased rate of premature birth, altered fetal pancreatic function, insulin signalling and amino acid metabolism, and also alterations in maternal adaptation to pregnancy. We are currently studying the postnatal consequences of these changes. Other research groups have shown that restricted nutrition of sheep in the early part of pregnancy alters postnatal muscle development, fat deposition, cardiovascular regulation and HPAA function. One aim of this review is to illustrate how biomedical research using animals such as the sheep has been used to gain a better understanding of the consequences of reduced maternal nutrition during the periconceptional period. We suggest that there are equally important consequences of this research for the livestock production industries.

Gestation length in red deer: genetically determined or environmentally controlled?

The red deer (Cervus elaphus) of European origin (e.g. subspecies scoticus, hispanicus, hippelaphus) is a medium sized (100-150kg mature hind weight) ruminant that exhibits highly seasonally patterns of autumn conceptions and summer births. Historic data indicate average (+/- s.d.) gestation length of 233-234 (+/- 2-4) days. Recently, however, there has been growing awareness that there is considerably greater variation in gestation length than earlier indicated and that there is a significant element of environmental, and possibly even social, control over the duration of pregnancy in this species. Imposition of variable levels of nutrition over late pregnancy of red deer hinds has been observed to influence fetal growth trajectory and gestation length, with no apparent effect on birth weight. This supports a hypothesis that under conditions of modest feed imbalance, variation in gestation length compensates for variation in fetal growth trajectory to ensure optimisation of birth weight. More recent studies on primiparous (24 month old) red deer hinds have identified surprisingly large variation in gestation length (193-263 days) compared with adult hinds (228-243 days), with earlier conceiving individuals within the primiparous cohort expressing significantly longer gestation than the later conceiving hinds, resulting in a higher level of calving synchrony than expected from known conception dates. This introduces an intriguing hypothesis of social indicative effects on parturition timing to promote within-cohort birth synchrony. Collectively, these data debunk the commonly held notion that gestation length of red deer is genetically fixed within strict limits. A review of the literature points to this as possibly a common phenomenon across a range of non-domesticated ruminant species but this conclusion is not supported by numerous conflicting studies on domestic sheep and cattle.

Fetal growth trajectories and their association with maternal and child characteristics

Background: The growth of the fetus is a complex process, influenced by genetic and environmental factors. Longitudinal patterns of fetal growth are required to fully understand this process, however to date, a paucity of data exists in this area.Objective: To identify fetal growth trajectories in-utero and to assess their association with maternal and child characteristics up to 5 years postnatal.Methods: Data from 781 mother–child pairs from the ROLO longitudinal birth cohort study were analyzed. The ROLO study was a randomized control trial of a low glycemic index diet in pregnancy to prevent recurrence of macrosomia. Fetal ultrasound measurements were recorded at 20 and 34 weeks gestation, and birth weight was recorded. Abdominal circumference (AC), weight (fetal weight, or birth weight), a standardized proxy for length (femur length or birth length, individually standardized), and AC:length ratio were examined for trajectory classes using latent class trajectory mixture models. Two-, three-, four-, and five-class models were evaluated for fit, using a linear (first order) trajectory over three time-points. ANOVA and chi-square tests were applied to test associations between trajectory membership and maternal and child characteristics up to age 5.Results: For AC, two fetal growth trajectories were identified, with 29% of participants on a “slow” trajectory and 71% on a “fast” trajectory. Those on a fast trajectory had higher rates of maternal impaired glucose tolerance (28.7 versus 16.5%, p<.001) and higher rates of mean child 5-year body mass index (BMI) centiles (64th versus 58th centile, p<.05) compared to those on the slow trajectory. For estimated fetal weight, four trajectories were identified, with 4% on a “very-slow” trajectory, 63% in a “moderate-slow” trajectory, 30% in a “moderate-fast” trajectory and 3% on a “very-fast” trajectory. Mothers with a fetus on the fastest trajectory had higher antenatal serum glucose levels (p<.05), and were more likely to deliver by cesarean section (59.1 versus 20%, p<.001). At 5 years of age, children on the fastest growth trajectory had the highest mean BMI centile (86th versus 60th centile, p<.05).Conclusions: This study shows that specific fetal growth trajectories may be associated with maternal serum glucose concentrations during pregnancy, mode of delivery and child BMI at 5 years of age. Diet and lifestyle measures that target maternal glucose levels during pregnancy may have lifelong benefits for children’s BMI. Identifying those on an accelerated growth trajectory during fetal life provides a unique opportunity for antenatal and infant interventions that may have long-lasting health benefits.

Percentiles of Pregnancy Outcomes with Maternal Age

Background: Maternal age is one of the prime factors in healthy pregnancy outcomes. Extremes of maternal age will lead to adverse effects on the growth trajectory of fetus and placenta. Hence, current study assessed the impact of maternal age with the percentiles of birth weight and placental morphometry. Materials and Method: Study was conducted on 391 subjects in a teaching hospital of North Karnataka, India for a period of 6 months. Ethical clearance was obtained. Data was collected by using standard pretested proforma. Percentiles of the birth weight and placental morphometry in different maternal age has been expressed in table, and Box plots have been plotted. Result: Age-wise distribution of 391 mothers reveals that 7.2 percents were less than 20 years of age and 7.6 percent more than 30 years and above, with mean 23.6 and SD 3.7 years. Percentiles of the birth weight and placental morphometry did not show any consistent relationship with increasing groups of age. Conclusion: The study conveys that in different groups of maternal age percentiles of birth weight exhibited consistent increasing trends only in higher percentiles (75th to 95th) whereas, percentiles of placental morphometry did not exhibit consistent relationship with mother’s age.

Novel roles of mechanistic target of rapamycin signaling in regulating fetal growth†.

Mechanistic target of rapamycin (mTOR) signaling functions as a central regulator of cellular metabolism, growth, and survival in response to hormones, growth factors, nutrients, energy, and stress signals. Mechanistic TOR is therefore critical for the growth of most fetal organs, and global mTOR deletion is embryonic lethal. This review discusses emerging evidence suggesting that mTOR signaling also has a role as a critical hub in the overall homeostatic control of fetal growth, adjusting the fetal growth trajectory according to the ability of the maternal supply line to support fetal growth. In the fetus, liver mTOR governs the secretion and phosphorylation of insulin-like growth factor binding protein 1 (IGFBP-1) thereby controlling the bioavailability of insulin-like growth factors (IGF-I and IGF-II), which function as important growth hormones during fetal life. In the placenta, mTOR responds to a large number of growth-related signals, including amino acids, glucose, oxygen, folate, and growth factors, to regulate trophoblast mitochondrial respiration, nutrient transport, and protein synthesis, thereby influencing fetal growth. In the maternal compartment, mTOR is an integral part of a decidual nutrient sensor which links oxygen and nutrient availability to the phosphorylation of IGFBP-1 with preferential effects on the bioavailability of IGF-I in the maternal-fetal interface and in the maternal circulation. These new roles of mTOR signaling in the regulation fetal growth will help us better understand the molecular underpinnings of abnormal fetal growth, such as intrauterine growth restriction and fetal overgrowth, and may represent novel avenues for diagnostics and intervention in important pregnancy complications.

Gestational diabetes and ultrasound-assessed fetal growth in South Asian and White European women: findings from a prospective pregnancy cohort

BackgroundMaternal gestational diabetes (GDM) is an established risk factor for large size at birth, but its influence on intrauterine fetal growth in different ethnic populations is less well understood. Here, we examine the joint associations of GDM and ethnicity with longitudinal fetal growth in South Asian and White European origin women.MethodsThis study included 10,705 singletons (4747 White European and 5958 South Asian) from a prospective cohort of women attending an antenatal clinic in Bradford, in the North of England. All women completed a 75-g oral glucose tolerance test at 26–28 weeks’ gestation. Ultrasound measurements of fetal head circumference (HC), femur length (FL) abdominal circumference (AC), and estimated fetal weight (EFW), and corresponding anthropometric measurements at birth were used to derive fetal growth trajectories. Associations of GDM and ethnicity with these trajectories were assessed using multilevel fractional polynomial models.ResultsEight hundred thirty-two pregnancies (7.8%) were affected by GDM: 10.4% of South Asians and 4.4% of White Europeans. GDM was associated with a smaller fetal size in early pregnancy [differences (95% CI) in mean HC at 12 weeks and mean AC and EFW at 16 weeks comparing fetuses exposed to GDM to fetuses unexposed (reference) = − 1.8 mm (− 2.6; − 1.0), − 1.7 mm (− 2.5; − 0.9), and − 6 g (− 10; − 2)] and a greater fetal size from 24 weeks’ gestation through to term [differences (95% CI) in mean HC, AC, and EFW comparing fetuses exposed to GDM to those unexposed = 0.9 mm (0.3; 1.4), 0.9 mm (0.2; 1.7), and 7 g (0; 13) at 24 weeks]. Associations of GDM with fetal growth were of similar magnitude in both ethnic groups. Growth trajectories, however, differed by ethnicity with South Asians being smaller than White Europeans irrespective of GDM status. Consequently, South Asian fetuses exposed to GDM were smaller across gestation than fetuses of White Europeans without GDM.ConclusionsIn both ethnic groups, GDM is associated with early fetal size deviations prior to GDM diagnosis, highlighting the need for novel strategies to diagnose pregnancy hyperglycemia earlier than current methods. Our findings also suggest that ethnic-specific fetal growth criteria are important in identifying hyperglycemia-associated pathological effects.

Neuronatin deletion causes postnatal growth restriction and adult obesity in 129S2/Sv mice

ObjectiveImprinted genes are crucial for the growth and development of fetal and juvenile mammals. Altered imprinted gene dosage causes a variety of human disorders, with growth and development during these crucial early stages strongly linked with future metabolic health in adulthood. Neuronatin (Nnat) is a paternally expressed imprinted gene found in neuroendocrine systems and white adipose tissue and is regulated by the diet and leptin. Neuronatin expression is downregulated in obese children and has been associated with stochastic obesity in C57BL/6 mice. However, our recent studies of Nnat null mice on this genetic background failed to display any body weight or feeding phenotypes but revealed a defect in glucose-stimulated insulin secretion due to the ability of neuronatin to potentiate signal peptidase cleavage of preproinsulin. Nnat deficiency in beta cells therefore caused a lack of appropriate storage and secretion of mature insulin. MethodsTo further explore the potential role of Nnat in the regulation of body weight and adiposity, we studied classical imprinting-related phenotypes such as placental, fetal, and postnatal growth trajectory patterns that may impact upon subsequent adult metabolic phenotypes. ResultsHere we find that, in contrast to the lack of any body weight or feeding phenotypes on the C57BL/6J background, deletion of Nnat in mice on 129S2/Sv background causes a postnatal growth restriction with reduced adipose tissue accumulation, followed by catch up growth after weaning. This was in the absence of any effect on fetal growth or placental development. In adult 129S2/Sv mice, Nnat deletion was associated with hyperphagia, reduced energy expenditure, and partial leptin resistance. Lack of neuronatin also potentiated obesity caused by either aging or high fat diet feeding. ConclusionsThe imprinted gene Nnat plays a key role in postnatal growth, adult energy homeostasis, and the pathogenesis of obesity via catch up growth effects, but this role is dependent upon genetic background.

Comparison of the INTERGROWTH-21st, National Institute of Child Health and Human Development, and WHO fetal growth standards.

To compare the ability of the INTERGROWTH-21st, National Institute of Child Health and Human Development, and WHO fetal growth standards to identify fetuses at risk of adverse perinatal outcomes. A retrospective analysis was performed among women enrolled in a multicenter randomized controlled trial (Routine Antenatal Diagnostic Imaging with Ultrasound) that was conducted in six states in the USA between November 1987 and May 1991. The predictive capability of various biometric indicators (biparietal diameter, femur length, abdominal circumference, head circumference, estimated fetal weight, and birthweight) was evaluated. Adverse outcomes included severe morbidity and perinatal death. There were 9409 women included. Biometric indicators measured at a gestational age of 18-24 weeks had insufficient predictive sensitivity (range, 4%-47%). By contrast, measurements taken at 28-34 weeks predicted statistically significant relative risk (range 1.5-10.2; P<0.05 for 27/30 relative risk values) and area under the receiver operating characteristic curve (range, 0.50-0.59; P<0.05 for 8/15 curves). Nonetheless, differences in accuracy between standards for predicting adverse perinatal outcomes were subtle (P>0.05 for differences in area under the curve values). Although useful to monitor fetal growth trajectory and the level of risk, all three fetal growth standards provided limited accuracy for identifying fetuses at risk of adverse perinatal outcomes.

A joint design for functional data with application to scheduling ultrasound scans

A joint design for sampling functional data is proposed to achieve optimal prediction of both functional data and a scalar outcome. The motivating application is fetal growth, where the objective is to determine the optimal times to collect ultrasound measurements in order to recover fetal growth trajectories and to predict child birth outcomes. The joint design is formulated using an optimization criterion and implemented in a pilot study. Performance of the proposed design is evaluated via simulation study and application to fetal ultrasound data.

509: The association between fetal growth trajectories and adverse neonatal outcomes in a preterm population

Customized fetal growth trajectories have been suggested as an alternative to arbitrary thresholds to identify pathologically growth-restricted fetuses (FGR). The objective of this study was to estimate the risk of adverse neonatal outcomes using fetal growth trajectories in the preterm neonate. This is a retrospective cohort study of non-anomalous singleton gestations that underwent a mean of three ultrasounds in our unit between 20-40 weeks gestation from 2008-2015. Growth trajectories were created from estimated fetal weights (EFW) using growth mixture models. Fetuses were classified as having either decelerated, normal or accelerated growth trajectories. Analysis was limited to fetuses delivered between 28-36 weeks that were admitted to the neonatal intensive care unit. The primary outcome was a composite neonatal morbidity. Secondary outcomes included actual birth weight (BW), 5 minute Apgar scores, and respiratory distress syndrome (RDS). Univariate and multivariate logistic regression analyses were used to estimate the risk of adverse neonatal outcomes across fetal growth trajectories. Of 355 fetuses, growth trajectories were identified as decelerated in 46.5%, normal in 49.3% and accelerated in 4.2%. Compared to fetuses with normal growth, fetuses with decelerated growth had an increased risk of having an actual BW<10th percentile, actual BW<5th percentile and 5 minute Apgar score <7. (Table) After adjusting for gestational age at the time of delivery, a decelerated fetal growth trajectory was significantly associated with an increased risk for the composite adverse neonatal outcome (aOR 1.7, 95% CI 1.1-2.9). Only 12.7% of patients with a decelerated growth trajectory would have been identified as FGR by EFW<10th percentile at the last ultrasound prior to delivery. A decelerated fetal growth trajectory is associated with an increased risk for adverse neonatal outcomes in a preterm population. This approach may more accurately identify fetuses with abnormal growth which ultimately may influence patient counseling and fetal surveillance.

125: Fetal growth trajectories

To identify fetal growth trajectories and to assess their association with maternal and child characteristics using baseline and 5-year post-partum follow up data from a randomised control trial of low glycaemic index diet in secundigravida patients with a previous baby >4kg ROLO study. The ROLO recorded fetal ultrasound measurements at 20 and 34 week’s gestation, and birth weight. Abdominal Circumference (AC), weight (Hadlock 4 Estimated Fetal Weight, or birth weight), a standardised proxy for length (femur length or birth length, individually standardised), and AC:length ratio (using standardised length proxy) were examined for trajectory classes using latent class trajectory mixture models. Two-, three-, four-, and five-class models were evaluated for fit, using a linear (first order) trajectory over three time-points. ANOVA and chi-square tests were applied to test associations between trajectory membership and maternal and age 5 child characteristics. No distinguishable classes were detected for Length. For abdominal circumference (AC), two fetal growth trajectories were identified, with 29% of participants on a slow trajectory and 71% on a fast trajectory. Those on a fast trajectory had higher rates of maternal impaired glucose tolerance (28.7% vs 16.5%, p<0.001) and higher rates of mean child 5 year BMI centiles (64th vs 58th centile, p<0.05) compared to those on the slow trajectory. For estimated fetal weight, four trajectories were identified, with 4% on a very slow trajectory, 63% in a moderate slow trajectory, 30% in a moderate-fast trajectory and 3% on a very fast trajectory (see figure). Mothers with a fetus on the fastest trajectory had a significantly higher BMI (mean 30 vs 26 p<0.002) higher antenatal glucose levels (p<0.05) and were more likely to deliver by caesarean section (59.1% vs 20%, p<0.001). At 5 year follow up, children on the fastest growth trajectory had the highest mean BMI centile (see table). This study shows specific fetal growth trajectories are associated with maternal BMI and maternal serum glucose, mode of delivery and child BMI. Diet and lifestyle measures that target maternal glucose levels during pregnancy may have lifelong benefits for children’s BMI. Identifying those on an accelerated growth trajectory during fetal life provides a unique opportunity for antenatal and infant interventions that may have long-lasting health benefits.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

520: Analysis of the fetal growth trajectory improves risk stratification in growth-restricted fetuses

520: Analysis of the fetal growth trajectory improves risk stratification in growth-restricted fetuses

Fetal somatic growth trajectory differs by type of congenital heart disease.

BackgroundThe growth trajectories of common measurements, including estimated fetal weight (EFW), head circumference (HC), and abdominal circumference (AC), in fetuses with congenital heart disease (CHD) have not been described for different cardiac lesions. We hypothesized that (i) fetuses with CHD have differential growth in utero, and (ii) different categories of CHD demonstrate different in utero growth curves.MethodsWe performed a retrospective observational cohort study of pregnancies with known fetal CHD seen from January 2000 to June 2013. For analysis, the infants were divided into single ventricle (SV), biventricular conotruncal, d-transposition of great arteries (d-TGA), biventricular septal defects (SD; including atrial, ventricular, and atrioventricular SD), and all others (Other).ResultsA total of 194 newborns met inclusion criteria. There was significant differential growth of EFW in all CHD types, except d-TGA, starting with low z-scores before 25 weeks gestation, improving toward normal around 30-32 weeks gestation, and then again differential growth with advancing gestation. SV and SD groups had significant differential growth of HC starting early in gestation and linearly progressing negative z-scores with advancing gestation.ConclusionWe observed differences in the fetal growth curves throughout gestation for the major categories of CHD, including significant differential growth in even "simple" CHD, such as SD.

Association of Maternal Obesity With Longitudinal Ultrasonographic Measures of Fetal Growth

Despite the increasing prevalence of pregravid obesity, systematic evaluation of the association of maternal obesity with fetal growth trajectories is lacking. To characterize differences in fetal growth trajectories between obese and nonobese pregnant women, and to identify the timing of any observed differences. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons study enrolled cohorts of pregnant women at 12 US health care institutions. Obese women (with prepregnancy body mass index > 30) and nonobese women (prepregnancy body mass indexes, 19-29.9) without major chronic diseases were recruited between 8 weeks and 0 days' gestation and 13 weeks and 6 days' gestation. A mixed longitudinal randomization scheme randomized participants into 1 of 4 schedules for 2-dimensional and 3-dimensional ultrasonograms to capture weekly fetal growth data throughout the remainder of their pregnancies. On each ultrasonogram, fetal humerus length, femur length, biparietal diameter, head circumference, and abdominal circumference were measured. Fetal growth curves were estimated using linear mixed models with cubic splines. Median differences in the fetal measures at each gestational week of the obese and nonobese participants were examined using the likelihood ratio and Wald tests after adjustment for maternal characteristics. The study enrolled 468 obese and 2334 nonobese women between 8 weeks and 0 days' gestation and 13 weeks and 6 days' gestation. After a priori exclusion criteria, 443 obese and 2320 nonobese women composed the final cohort. Commencing at 21 weeks' gestation, femur length and humerus length were significantly longer for fetuses of obese woman than those of nonobese women. Differences persisted in obese and nonobese groups through 38 weeks' gestation (median femur length, 71.0 vs 70.2 mm; P = .01; median humerus length, 62.2 vs 61.6 mm; P = .03). Averaged across gestation, head circumference was significantly larger in fetuses of obese women than those of nonobese women (P = .02). Fetal abdominal circumference was not greater in the obese cohort than in the nonobese cohort but was significantly larger than in fetuses of normal-weight women (with body mass indexes between 19.0-24.9) commencing at 32 weeks (median, 282.1 vs 280.2 mm; P = .04). Starting from 30 weeks' gestation, estimated fetal weight was significantly larger for the fetuses of obese women (median, 1512 g [95% CI, 1494-1530 g] vs 1492 g [95% CI, 1484-1499 g]) and the difference grew as gestational age increased. Birth weight was higher by almost 100 g in neonates born to obese women than to nonobese women (mean, 3373.2 vs 3279.5 g). As early as 32 weeks' gestation, fetuses of obese women had higher weights than fetuses of nonobese women. The mechanisms and long-term health implications of these findings are not yet established.

Sex differences in rat placental development: from pre-implantation to late gestation

BackgroundA male fetus is suggested to be more susceptible to in utero and birth complications. This may be due in part to altered morphology or function of the XY placenta. We hypothesised that sexual dimorphism begins at the blastocyst stage with sex differences in the progenitor trophectoderm (TE) and its derived trophoblast lineages, as these cells populate the majority of cell types within the placenta. We investigated sex-specific differences in cell allocation in the pre-implantation embryo and further characterised growth and gene expression of the placental compartments from the early stages of the definitive placenta through to late gestation.MethodsNaturally mated Sprague Dawley dams were used to collect blastocysts at embryonic day (E) 5 to characterise cell allocation; total, TE, and inner cell mass (ICM), and differentiation to downstream trophoblast cell types. Placental tissues were collected at E13, E15, and E20 to characterise volumes of placental compartments, and sex-specific gene expression profiles.ResultsPre-implantation embryos showed no sex differences in cell allocation (total, TE and ICM) or early trophoblast differentiation, assessed by outgrowth area, number and ploidy of trophoblasts and P-TGCs, and expression of markers of trophoblast stem cell state or differentiation. Whilst no changes in placental structures were found in the immature E13 placenta, the definitive E15 placenta from female fetuses had reduced labyrinthine volume, fetal and maternal blood space volume, as well as fetal blood space surface area, when compared to placentas from males. No differences between the sexes in labyrinth trophoblast volume or interhaemal membrane thickness were found. By E20 these sex-specific placental differences were no longer present, but female fetuses weighed less than their male counterparts. Coupled with expression profiles from E13 and E15 placental samples may suggest a developmental delay in placental differentiation.ConclusionsAlthough there were no overt differences in blastocyst cell number or early placental development, reduced growth of the female labyrinth in mid gestation is likely to contribute to lower fetal weight in females at E20. These data suggest sex differences in fetal growth trajectories are due at least in part, to differences in placenta growth.

Fetal growth trajectories in pregnancies of European and South Asian mothers with and without gestational diabetes, a population-based cohort study.

ObjectiveOur aim was to examine the impact of gestational diabetes (GDM), from before the GDM-diagnosis is made, on fetal growth trajectories, and to compare it in Europeans and South Asians; two ethnic groups with dissimilar fetal growth patterns.MethodsWe studied European (n = 349) and South Asian (n = 184) pregnant women, from the population-based STORK-Groruddalen cohort in Oslo, Norway. Mothers were enrolled in early pregnancy, screened for GDM in gestational week 28 ±2, and classified as “non-GDM”, “mild GDM” or “moderate/severe GDM”. We measured fetal head circumference, abdominal circumference and femur length by ultrasound, and estimated fetal weight in gestational week 24, 32 and 37, and performed corresponding measurements at birth.ResultsIn non-GDM pregnancies, South Asian fetuses (n = 156) had a slower growth from gestational week 24, compared with Europeans (n = 310). More than two thirds of the European mothers later diagnosed with GDM were overweight or obese in early pregnancy, while this was not observed in South Asians. Fetuses of GDM mothers tended to be smaller than fetuses of non-GDM mothers in week 24, but thereafter grew faster until birth. This pattern was especially pronounced in fetuses of South Asian mothers with moderate/severe GDM. In week 24 these fetuses had a -0.95 SD (95% CI: -1.53, -0.36) lower estimated fetal weight than their non-GDM counterparts. In contrast, at birth they were 0.45 SD (0.09, 0.81) larger.ConclusionsOffspring of GDM mothers were smaller in mid pregnancy, but subsequently grew faster until birth, compared with offspring of non-GDM mothers. This pattern was most prominent in South Asian mothers with moderate to severe GDM. However, the most remarkable characteristic of these fetuses was not a large size at birth, but the small size in mid pregnancy, before the GDM diagnosis was set.

A role for maternally derived myokines to optimize placental function and fetal growth across gestation.

Exercise during pregnancy is associated with improved health outcomes for both mother and baby, including a reduced risk of future obesity and susceptibility to chronic diseases. Overwhelming evidence demonstrates a protective effect of maternal exercise against fetal birth weight extremes, reducing the rates of both large- and small-for-gestational-age infants. It is speculated that this protective effect is mediated in part through exercise-induced regulation of maternal physiology and placental development and function. However, the specific mechanisms through which maternal exercise regulates these changes remain to be discovered. We hypothesize that myokines, a collection of peptides and cytokines secreted from contracting skeletal muscles during exercise, may be an important missing link in the story. Myokines are known to reduce inflammation, improve metabolism and enhance macronutrient transporter expression and activity in various tissues of nonpregnant individuals. Little research to date has focused on the specific roles of the myokine secretome in the context of pregnancy; however, it is likely that myokines secreted from exercising skeletal muscles may modulate the maternal milieu and directly impact the vital organ of pregnancy-the placenta. In the current review, data in strong support of this potential role of myokines will be presented, suggesting myokine secretion as a key mechanism through which maternal exercise optimizes fetal growth trajectories. It is clear that further research is warranted in this area, as knowledge of the biological roles of myokines in the context of pregnancy would better inform clinical recommendations for exercise during pregnancy and contribute to the development of important therapeutic interventions.

651: Fetal growth trajectories and relationship to time to delivery: the NICHD fetal growth studies

651: Fetal growth trajectories and relationship to time to delivery: the NICHD fetal growth studies

Exploring sexual dimorphism in placental circulation at 22–24 weeks of gestation: A cross-sectional observational study

IntroductionPlacental blood flow is closely associated with fetal growth and wellbeing. Recent studies suggest that there are differences in blood flow between male and female fetuses. We hypothesized that sexual dimorphism exists in fetal and placental blood flow at 22–24 weeks of gestation. MethodsThis was a prospective cross-sectional study of 520 healthy pregnant women. Blood flow velocities of the middle cerebral artery (MCA), umbilical artery (UA), umbilical vein (UV) and the uterine arteries (UtA) were measured using Doppler ultrasonography. UV and UtA diameters were measured using two-dimensional ultrasonography and power Doppler angiography. Volume blood flows (Q) of the UV and UtA were calculated. Maternal haemodynamics was assessed with impedance cardiography. UtA resistance (Ruta) was computed as MAP/Quta. ResultsUA PI was significantly (p = 0.008) higher in female fetuses (1.19 ± 0.15) compared with male fetuses (1.15 ± 0.14). MCA PI, cerebro-placental ratio (MCA PI/UA PI), Quv, UtA PI, Quta and Ruta were not significantly different between groups. At delivery, the mean birth weight and placental weight of female infants (3504 g and 610 g) were significantly (p = 0.0005 and p = 0.039) lower than that of the male infants (3642 g and 634 g). DiscussionWe have demonstrated sexual dimorphism in UA PI, a surrogate for placental vascular resistance, at 22–24 weeks of gestation. Therefore, it would be useful to know when this difference emerges and whether it translates into blood flow differences that may impact upon the fetal growth trajectory.