Variation In Fetal Growth Research Articles

Correlation between Gestational Age and Head Circumference in Third Trimester

Introduction: In today’s advanced medical world maternal child health care the important part of the healthcare system and import components is estimation fetal gestational age.Gestational age is age of unborn baby, defined in weeks as beginning from first day of last menstrualperiod prior to conception. Trimester is period of three calendar months during a pregnancy. Clinically, thegestational period is divided into three trimesters. Estimation of gestational age and thereby forecastingexpected date of delivery (EDD) is not only concern of the Individual but it is invaluable in the diagnosis ofintrauterine growth retardation of fetus and obstetric planning other fetal parameters are useful Hence; weplanned the present study to estimate fetal HC length for measuring the gestational age and compare it withother parameters.Material and methods: The study Correlation between gestational age and head circumference in Thirdtrimester was carried out at Govt. Medical College and Hospital, Nanded, between July 2011 to July 2013period . The study included 132 pregnant women the data so collected was then subjected to statisticalanalysis by expert statistician with the help of SYSTAT Crainsoft version 12 software. Standard statisticalmethods, parametric methods were used for the evaluation and significance.Results: As the value of R is 0.8612, the variation in fetal growth on the basis of Head Circumference duringthird trimester can be explained to the extent of 86.12%. The value of R is highly significant (Student’s‘t’test value = 228.92, p<0.0001, very highly significant) showing that there is statistically highly Positive orstrong positive association between gestational age and head CircumferenceConclusion: From the present study Head Circumference found to be statistically highly significant. Theregression equations derived for growth parameter for estimating gestational age in a normally developingfetus, increase with gestational age, showed good correlation with gestational age. In Present study, Headcircumference is the sensitive parameter and a result of present study was comparable with previous studies.

Risk of spontaneous preterm birth and fetal growth associates with fetal SLIT2.

Spontaneous preterm birth (SPTB) is the leading cause of neonatal death and morbidity worldwide. Both maternal and fetal genetic factors likely contribute to SPTB. We performed a genome-wide association study (GWAS) on a population of Finnish origin that included 247 infants with SPTB (gestational age [GA] < 36 weeks) and 419 term controls (GA 38–41 weeks). The strongest signal came within the gene encoding slit guidance ligand 2 (SLIT2; rs116461311, minor allele frequency 0.05, p = 1.6×10−6). Pathway analysis revealed the top-ranking pathway was axon guidance, which includes SLIT2. In 172 very preterm-born infants (GA <32 weeks), rs116461311 was clearly overrepresented (odds ratio 4.06, p = 1.55×10−7). SLIT2 variants were associated with SPTB in another European population that comprised 260 very preterm infants and 9,630 controls. To gain functional insight, we used immunohistochemistry to visualize SLIT2 and its receptor ROBO1 in placentas from spontaneous preterm and term births. Both SLIT2 and ROBO1 were located in villous and decidual trophoblasts of embryonic origin. Based on qRT-PCR, the mRNA levels of SLIT2 and ROBO1 were higher in the basal plate of SPTB placentas compared to those from term or elective preterm deliveries. In addition, in spontaneous term and preterm births, placental SLIT2 expression was correlated with variations in fetal growth. Knockdown of ROBO1 in trophoblast-derived HTR8/SVneo cells by siRNA indicated that it regulate expression of several pregnancy-specific beta-1-glycoprotein (PSG) genes and genes involved in inflammation. Our results show that the fetal SLIT2 variant and both SLIT2 and ROBO1 expression in placenta and trophoblast cells may be correlated with susceptibility to SPTB. SLIT2-ROBO1 signaling was linked with regulation of genes involved in inflammation, PSG genes, decidualization and fetal growth. We propose that this receptor-ligand couple is a component of the signaling network that promotes SPTB.

Genetic and Environmental Influences on Fetal Growth Vary during Sensitive Periods in Pregnancy

Aberrant fetal growth is associated with morbidities and mortality during childhood and adult life. Although genetic and environmental factors are known to influence in utero growth, their relative contributions over pregnancy is unknown. We estimated, across gestation, the genetic heritability, contribution of shared environment, and genetic correlations of fetal growth measures (abdominal circumference (AC), humerus length (HL), femur length (FL), and estimated fetal weight (EFW)) in a prospective cohort of dichorionic twin gestations recruited through the NICHD Fetal Growth Studies. Structural equation models were fit at the end of first trimester, during mid-gestation, late second trimester, and third trimester of pregnancy. The contribution of fetal genetics on fetal size increased with gestational age, peaking in late second trimester (AC = 53%, HL = 57%, FL = 72%, EFW = 71%; p < 0.05). In contrast, shared environment explained most of phenotypic variations in fetal growth in the first trimester (AC = 50%, HL = 54%, FL = 47%, EFW = 54%; p < 0.05), suggesting that the first trimester presents an intervention opportunity for a more optimal early fetal growth. Genetic correlations between growth traits (range 0.34–1.00; p < 0.05) were strongest at the end of first trimester and declined with gestation, suggesting that different fetal growth measures are more likely to be influenced by the same genes in early pregnancy.

What birthweight percentile is associated with optimal perinatal mortality and childhood education outcomes?

Small for gestational age, defined as birthweight <10th percentile for gestational age, is known to be associated with clinically meaningful impairments in health and development. The effects of variation within the normal range of birthweight percentile on perinatal mortality and childhood education remain less well defined. We sought to quantify the association among birthweight percentile, perinatal mortality, and educational outcomes and to determine the optimal birthweight percentile for those outcomes in Aboriginal and non-Aboriginal Australian children. This was a retrospective cohort study. Perinatal data for all children born in the Northern Territory, Australia, from 1999 through 2008 were linked to measures of educational attainment at age 8-9 years. Multivariable analysis was used to determine the optimal birthweight percentile for low perinatal mortality and high reading and numeracy scores. The birth cohort contained 35,239 births (42% Aboriginal), of which 11,214 had linked and valid education records. Median birthweight percentile was 29.2 in Aboriginal infants and 44.0 in non-Aboriginal infants. The odds of perinatal mortality decreased by 4% with each 1-percentile increase birthweight percentile overall (adjusted odds ratio, 0.96; P= .000) and lowest mortality rates were at the 61st and 78th percentile in Aboriginal and non-Aboriginal infants, respectively. Although birthweights <10th percentile were associated with greatly increased odds of perinatal mortality, the increased risk extended well beyond this cut-off. Birthweight percentile was also positively correlated with scores in reading (P= .000) and numeracy (P= .000). In non-Aboriginal children, reading and numeracy scores peaked at the 66th percentile, but for Aboriginal children there was continuous benefit with increasing birthweight percentile. Birthweight percentile explained 1% of the variation in education outcomes, with much greater variation explained by other perinatal and sociodemographic factors. Birthweights between the 50th-93rd percentiles were most consistently associated with both low perinatal mortality and high reading and numeracy scores, suggesting that small for gestational age does not sufficiently capture the risks associated with variation in fetal growth. Our data indicate that the effect of birthweight percentile accounts for 1% of variation in perinatal and education outcomes.

Transabdominal Ultrasound for Pregnancy Diagnosis in Reeves' Muntjac Deer

Reeves' muntjac deer (Muntiacus reevesi) are a small cervid species native to southeast Asia, and are currently being investigated as a potential model of prion disease transmission and pathogenesis. Vertical transmission is an area of interest among researchers studying infectious diseases, including prion disease, and these investigations require efficient methods for evaluating the effects of maternal infection on reproductive performance. Ultrasonographic examination is a well-established tool for diagnosing pregnancy and assessing fetal health in many animal species1-7, including several species of farmed cervids8-19, however this technique has not been described in Reeves' muntjac deer. Here we describe the application of transabdominal ultrasound to detect pregnancy in muntjac does and to evaluate fetal growth and development throughout the gestational period. Using this procedure, pregnant animals were identified as early as 35 days following doe-buck pairing and this was an effective means to safely monitor the pregnancy at regular intervals. Future goals of this work will include establishing normal fetal measurement references for estimation of gestational age, determining sensitivity and specificity of the technique for diagnosing pregnancy at various stages of gestation, and identifying variations in fetal growth and development under different experimental conditions.

Transabdominal Ultrasound for Pregnancy Diagnosis in Reeves' Muntjac Deer

Reeves' muntjac deer (Muntiacus reevesi) are a small cervid species native to southeast Asia, and are currently being investigated as a potential model of prion disease transmission and pathogenesis. Vertical transmission is an area of interest among researchers studying infectious diseases, including prion disease, and these investigations require efficient methods for evaluating the effects of maternal infection on reproductive performance. Ultrasonographic examination is a well-established tool for diagnosing pregnancy and assessing fetal health in many animal species(1-7), including several species of farmed cervids(8-19), however this technique has not been described in Reeves' muntjac deer. Here we describe the application of transabdominal ultrasound to detect pregnancy in muntjac does and to evaluate fetal growth and development throughout the gestational period. Using this procedure, pregnant animals were identified as early as 35 days following doe-buck pairing and this was an effective means to safely monitor the pregnancy at regular intervals. Future goals of this work will include establishing normal fetal measurement references for estimation of gestational age, determining sensitivity and specificity of the technique for diagnosing pregnancy at various stages of gestation, and identifying variations in fetal growth and development under different experimental conditions.

No association between body size at birth and leucocyte telomere length in adult life--evidence from three cohort studies

Shorter leucocyte telomere length (LTL) is a promising marker of biological ageing. It is predicted by cumulative adverse conditions throughout life course, but few studies have data from the prenatal period when most developmental processes and cell replication take place. We studied whether body size at birth and underlying factors including severely preterm birth predict LTL in adult life. We used data from following three cohorts: (i) 1894 subjects (age: 56-69 years) from the Helsinki Birth Cohort Study (HBCS), representing normal variation in fetal growth; (ii) the Helsinki Study of Very Low Birth Weight Adults encompassing 164 subjects born preterm at very low birthweight (<1500 g; representing extreme pre- and neonatal conditions) and 170 term-born controls (18-27 years) and (iii) 248 twins (23-31 years) from the FinnTwin16 cohort, allowing comparisons between twin pairs. Relative telomere length was measured from leucocytes by real-time quantitative polymerase chain reaction. Shorter LTL was associated with higher age in HBCS and among men in the Helsinki Study of Very Low Birth Weight Adults and with lower childhood socio-economic status in HBCS and FinnTwin16. LTL was not associated with weight, length or gestational age at birth in any cohort. LTL was similar in very-low-birthweight and control subjects. LTL is unlikely to be a useful marker of a mechanism linking body size at birth with individual differences in ageing in the general population.

Executive functions of six-year-old boys with normal birth weight and gestational age.

Impaired fetal development, reflected by low birth weight or prematurity, predicts an increased risk for psychopathology, especially attention deficit hyperactivity disorder (ADHD). Such effects cut across the normal range of birth weight and gestation. Despite the strength of existing epidemiological data, cognitive pathways that link fetal development to mental health are largely unknown. In this study we examined the relation of birth weight (>2500 g) and gestational age (37–41 weeks) within the normal range with specific executive functions in 195 Singaporean six-year-old boys of Chinese ethnicity. Birth weight adjusted for gestational age was used as indicator of fetal growth while gestational age was indicative of fetal maturity. Linear regression revealed that increased fetal growth within the normal range is associated with an improved ability to learn rules during the intra/extra-dimensional shift task and to retain visual information for short period of time during the delayed matching to sample task. Moreover, faster and consistent reaction times during the stop-signal task were observed among boys born at term, but with higher gestational age. Hence, even among boys born at term with normal birth weight, variations in fetal growth and maturity showed distinct effects on specific executive functions.

Seasonal variation in fetal growth: accounting for sociodemographic, biological, and environmental exposures

We sought to investigate seasonal variation in fetal growth, accounting for important sociodemographic, biological, and environmental exposures. Records of births 1998 through 2006 in Perth, Western Australia were obtained (N = 147,357). We investigated small for gestational age and sex and the proportion of optimal birthweight (POBW) in relation to seasonal exposures (season, temperature, sunlight) by trimester of pregnancy. Adjustment was made for a wide range of risk factors. The POBW for neonates with third trimesters predominantly in summer was 0.18% (0.00-0.36%) lower than for those in winter. POBW decreased by 0.14% (0.01-0.27%) per interquartile range increase in third-trimester temperature (9.15°C). An interquartile range increase in temperature over pregnancy (0.73°C) was associated with an odds ratio of 1.02 (95% confidence interval, 1.00-1.05) for small for gestational age and sex. Reduced fetal growth was associated with elevated ambient temperatures throughout and late in pregnancy, independently of air pollution and other risk factors.

Differential gene expressions in subcutaneous adipose tissue pointed to a delayed adipocytic differentiation in small pig fetuses compared to their heavier siblings

Intra-uterine growth retardation in piglets is associated to neonatal losses and a greater susceptibility to fat deposition in the long term. Dietary l-arginine supplementation to gilts during early gestation has been proposed as a way to enhance fetal survival. This study aims to investigate the effects of variation in fetal growth within litters and dietary l-arginine treatment during early gestation in pregnant sows on expression levels of several genes involved in early adipose tissue development and lipid deposition in the fetuses. At day 75 of pregnancy, sows fed a standard gestation diet throughout pregnancy and sows fed 26 g l-arginine daily from days 14 to 28 of gestation in supplement to the standard diet were sacrificed. Six pairs of littermates in each dietary group with the smallest or the heaviest fetal weights within each litter were collected (total: 24 fetuses). Expression levels of DLK1/ PREF1 and FZD7 were significantly greater in subcutaneous backfat of the smallest fetuses. Conversely, transcriptional adipogenic regulators PPARG, SREBP1, and CEBPA, and genes involved in terminal adipocytic differentiation LPL, ME1, and FABP4 were less expressed in those piglets. Fetal weight has no effect on expression levels of genes involved in cell cycle progression and DNA content in subcutaneous adipose tissue. Maternal dietary l-arginine treatment did not affect subcutaneous adipose tissue features in 75-day old fetuses. The gene expression changes observed in the smallest fetuses are likely associated to a lower body fat content at birth, and could predispose to catch-up fat growth during the postnatal period.

Recurring Complications in Second Pregnancy

OBJECTIVE: To clarify the obstetric consequences in a second pregnancy after a first singleton pregnancy complicated by spontaneous preterm delivery or preeclampsia and stratified by the variation in fetal growth. METHODS: In a registry-based cohort study, we identified women having a first and second singleton delivery in Denmark from 1978 to 2007 (n536,419). The exposures and endpoints were preterm delivery, preeclampsia, fetal growth, placental abruption, and stillbirth after 20 weeks of gestation. We used 2 and t test to compare differences between incidences on first and second pregnancies. RESULTS: Compared with a spontaneous first delivery at term, a delivery between 32 and 36 weeks of gestation increased the risk of preterm delivery in the second pregnancy from 2.7% to 14.7% (odds ratio [OR] 6.12, 95% confidence interval [CI] 5.84–6.42) and the risk of preeclampsia from 1.1% to 1.8% (OR 1.60, 95% CI 1.41–1.81); a delivery before 28 weeks increased the risk of a second preterm delivery to 26.0% (OR 13.1, 95% CI 10.8–15.9) and a second pregnancy with preeclampsia to 3.2% (OR 2.96, 95% CI 1.80–4.88). A first delivery in preeclamptic women between 32 and 36 weeks, compared with delivery after 37 weeks, increased the risk of preeclampsia in a second pregnancy from 14.1% to 25.3% (OR 2.08, 95% CI 1.87–2.31) and a small for gestational age infant from 3.1% to 9.6% (OR 2.82, 95% CI 2.38–3.35). Compared with the mean, fetal growth 2 to 3 standard deviations below mean in the first pregnancy increased the risk of preeclampsia from 1.1% to 1.8% (OR 1.62, 95% CI 1.34–1.96) in the second pregnancy. CONCLUSION: Spontaneous preterm delivery, preeclampsia, and fetal growth deviation tend to recur and predispose to each other in a second pregnancy. Severe complications further increase these risks. (Obstet Gynecol 2009;113:1217–24) LEVEL OF EVIDENCE: II

Prenatal Determinants of Uterine Volume and Ovarian Reserve in Adolescence

Adequate uterine volume and ovarian reserve are essential for reproductive health. Antenatal events such as restricted fetal growth and maternal tobacco smoking are hypothesized to impact on reproductive function in later life, although not studied in a large prospective normal pregnancy population to date. The objective of the study was to determine the relationship between intrauterine growth, birth weight, and maternal tobacco smoking on uterine volume and ovarian reserve in adolescence. This was a prospective study in which half the cohort underwent intensive ultrasound monitoring in utero. Intrauterine growth was measured using ultrasound at 18, 24, 28, and 34/36 wk gestation (n = 115 girls). Maternal smoking data were prospectively collected at 18 and 34/36 wk from the whole cohort. Uterine (n = 229) and early follicular ovarian volume and antral follicle count (n = 225) were measured using transabdominal ultrasound (n = 230). Ovarian reserve was estimated using early follicular phase anti-Mullerian hormone, inhibin B, and FSH (n = 213). The relationship between maternal tobacco smoking, intrauterine growth trajectories, and markers of ovarian reserve and uterine size in adolescence was measured. Linear regression showed that daughters of mothers who smoked had a significantly smaller uterus compared with nonsmokers (P = 0.019). No significant relationship between maternal tobacco smoking and ovarian volume (P = 0.164) or markers of ovarian reserve (antral follicle count, plasma FSH, anti-Mullerian hormone, and inhibin B) in adolescence was determined. Our findings indicate that maternal smoking, but not variations in fetal growth, may lead to a reduction in uterine volume and does not appear to impact ovarian reserve.

Recurring Complications in Second Pregnancy

To clarify the obstetric consequences in a second pregnancy after a first singleton pregnancy complicated by spontaneous preterm delivery or preeclampsia and stratified by the variation in fetal growth. In a registry-based cohort study, we identified women having a first and second singleton delivery in Denmark from 1978 to 2007 (n=536,419). The exposures and endpoints were preterm delivery, preeclampsia, fetal growth, placental abruption, and stillbirth after 20 weeks of gestation. We used chi and t test to compare differences between incidences on first and second pregnancies. Compared with a spontaneous first delivery at term, a delivery between 32 and 36 weeks of gestation increased the risk of preterm delivery in the second pregnancy from 2.7% to 14.7% (odds ratio [OR] 6.12, 95% confidence interval [CI] 5.84-6.42) and the risk of preeclampsia from 1.1% to 1.8% (OR 1.60, 95% CI 1.41-1.81); a delivery before 28 weeks increased the risk of a second preterm delivery to 26.0% (OR 13.1, 95% CI 10.8-15.9) and a second pregnancy with preeclampsia to 3.2% (OR 2.96, 95% CI 1.80-4.88). A first delivery in preeclamptic women between 32 and 36 weeks, compared with delivery after 37 weeks, increased the risk of preeclampsia in a second pregnancy from 14.1% to 25.3% (OR 2.08, 95% CI 1.87-2.31) and a small for gestational age infant from 3.1% to 9.6% (OR 2.82, 95% CI 2.38-3.35). Compared with the mean, fetal growth 2 to 3 standard deviations below mean in the first pregnancy increased the risk of preeclampsia from 1.1% to 1.8% (OR 1.62, 95% CI 1.34-1.96) in the second pregnancy. Spontaneous preterm delivery, preeclampsia, and fetal growth deviation tend to recur and predispose to each other in a second pregnancy. Severe complications further increase these risks. II.

Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth

The effect of high altitude on reducing birth weight is markedly less in populations of high- (e.g., Andeans) relative to low-altitude origin (e.g., Europeans). Uterine artery (UA) blood flow is greater during pregnancy in Andeans than Europeans at high altitude; however, it is not clear whether such blood flow differences play a causal role in ancestry-associated variations in fetal growth. We tested the hypothesis that greater UA blood flow contributes to the protection of fetal growth afforded by Andean ancestry by comparing UA blood flow and fetal growth throughout pregnancy in 137 Andean or European residents of low (400 m; European n = 28, Andean n = 23) or high (3,100-4,100 m; European n = 51, Andean n = 35) altitude in Bolivia. Blood flow and fetal biometry were assessed by Doppler ultrasound, and maternal ancestry was confirmed, using a panel of 100 ancestry-informative genetic markers (AIMs). At low altitude, there were no ancestry-related differences in the pregnancy-associated rise in UA blood flow, fetal biometry, or birth weight. At high altitude, Andean infants weighed 253 g more than European infants after controlling for gestational age and other known influences. UA blood flow and O(2) delivery were twofold greater at 20 wk in Andean than European women at high altitude, and were paralleled by greater fetal size. Moreover, variation in the proportion of Indigenous American ancestry among individual women was positively associated with UA diameter, blood flow, O(2) delivery, and fetal head circumference. We concluded that greater UA blood flow protects against hypoxia-associated reductions in fetal growth, consistent with the hypothesis that genetic factors enabled Andeans to achieve a greater pregnancy-associated rise in UA blood flow and O(2) delivery than European women at high altitude.

Maternal oxygen delivery is not related to altitude‐ and ancestry‐associated differences in human fetal growth

Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O(2) delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O(2) delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n=180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphism. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P<0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O(2) delivery regardless of ancestry. But the hypothesis was rejected as O(2) delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O(2) delivery, regardless of altitude (P<0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P<0.01), but admixture was not related to any of the O(2) transport variables. Genetically mediated differences in maternal O(2) delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O(2) and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry- and altitude-related differences in fetal growth. Uterine artery O(2) delivery in these pregnancies was 99 +/- 3 ml min(-1), approximately 5-fold greater than near-term fetal O(2) consumption. Deficits in maternal O(2) transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth.

Triplet Ultrasound Growth Parameters

To create ultrasound growth curves for normal growth of fetal triplets using statistical methodology that properly accounts for similarities of growth of fetuses within a mother as well as repeated measurements over time for each fetus. In this longitudinal study, all triplet pregnancies managed at a single tertiary center from 1992-2004 were reviewed. Fetuses with major anomalies, prior selective reduction, or fetal demise were excluded. Data from early and late gestation in which there were fewer than 30 fetal measurements available for analysis were excluded. We used multilevel models to account for variation in growth within a single fetus over time, variations in growth between multiple fetuses within a single mother, and variations in fetal growth between mothers. Medians (50th), 10th, and 90th percentiles were estimated by the creation of multiple quadratic growth models from bootstrap samples adapting a previously published method to compute prediction intervals. Estimated fetal weight was derived from Hadlock's formula. One hundred fifty triplet pregnancies were identified. Twenty-seven pregnancies were excluded for the following reasons: missing records (23), fetal demise (3), and fetal anomaly (1). The study group consisted of 123 pregnancies. The gestational age range was restricted to 14-34 weeks. Figures and tables were developed showing medians, 10th and 90th percentiles for estimated fetal weight, femur length, biparietal diameter, abdominal circumference, and head circumference. Growth curves for triplet pregnancies were derived. These may be useful for identification of abnormal growth in triplet fetuses. III.

Social variations in fetal growth in a Russian setting: an analysis of medical records.

The study examines variations in fetal growth by maternal social circumstances in a Russian town. All pregnant women registered at the antenatal clinics in 1999 in Severodvinsk (north-west Russia) and their live born infants comprised the study base (n=1399). Multivariate linear regression analysis was applied to quantify the effect of socio-demographic factors on birthweight and the ponderal index (PI). A clear gradient of birthweight in relation to mothers' education was revealed. Babies of the most educated mothers were 207 g (95% CI, 55, 358) heavier than babies of mothers with basic education. The average weight of those born to mothers with secondary and vocational levels of education was 172 g (95% CI, 91, 253) and 83 g (95% CI, 9, 163) lower compared with infants born to mothers with a university level of education after adjustment for age, parity, pre-pregnancy weight, marital status, maternal occupation, length of gestation, and sex of the baby. Maternal education also influenced the PI. Further studies should focus on the mechanisms of the coherence of maternal education and fetal growth. To ensure that all parts of the society benefit equally from economic and social reforms, social variations in pregnancy outcomes should be monitored during the time of transition.

Factors Influencing Fetal Growth

After completing this article, readers should be able to: 1. Describe the roles of insulin-like growth factor on fetal growth and development. 2. Delineate components of “maternal constraint.” 3. Explain the role of the placenta in regulating fetal growth. 4. Describe the effects of fetal glucose, amino acid, and fat supply on fetal growth. The principal determinants of fetal growth are fetal genotype and in utero environment. Environmental factors include maternal and paternal genetics, maternal size, and the capacity of the placenta to provide nutrients to the fetus. These environmental factors interact with the intrinsic growth pattern of the fetus, yielding a particular rate and composition of fetal growth. Most of the variation in fetal growth in a population is due to variations in environmental factors, not the fetal genome, although a genetically abnormal fetus clearly might not grow as well as a normal fetus if affected genes include those that are important for growth. Many genes contribute to fetal growth and birthweight. Techniques in which specific genes can either be deleted (“knockouts”) or overexpressed have led to greater understanding of how some of these genes regulate fetal growth. Such studies have shown that both maternal and paternal influences are present during fetal development and are passed on to the developing fetus by spermatozoa or oogonia by a mechanism called imprinting. Although the maternal genetic composition exerts greater influence than fetal genotype in the overall regulation of fetal growth, both maternal and paternal genomes are important in fetal growth and development (1)(2). For example, gynogenetic zygotes (two maternal genome copies) lead to underdeveloped extraembryonic tissues but well-developed embryos. The more modest regulation offered by the paternal genotype is essential for trophoblast development. For example, zygote nuclear transfer experiments have shown that androgenetic zygotes (two paternal genome copies) develop extensive trophoblast tissues but …

Mutations in the glucokinase gene of the fetus result in reduced birth weight.

Low birth weight and fetal thinness have been associated with non-insulin dependent diabetes mellitus (NIDDM) and insulin resistance in childhood and adulthood. It has been proposed that this association results from fetal programming in response to the intrauterine environment. An alternative explanation is that the same genetic influences alter both intrauterine growth and adult glucose tolerance. Fetal insulin secretion in response to maternal glycaemia plays a key role in fetal growth, and adult insulin secretion is a primary determinant of glucose tolerance. We hypothesized that a defect in the sensing of glucose by the pancreas, caused by a heterozygous mutation in the glucokinase gene, could reduce fetal growth and birth weight in addition to causing hyperglycaemia after birth. In 58 offspring, where one parent has a glucokinase mutation, the inheritance of a glucokinase mutation by the fetus resulted in a mean reduction of birth weight of 533 g (P=0.002). In 19 of 21 sibpairs discordant for the presence of a glucokinase mutation, the child with the mutation had a lower birth weight, with a mean difference of 521 g (P=0.0002). Maternal hyperglycaemia due to a glucokinase mutation resulted in a mean increase in birth weight of 601 g (P=0.001). The effects of maternal and fetal glucokinase mutations on birth weight were additive. We propose that these changes in birth weight reflect changes in fetal insulin secretion which are influenced directly by the fetal genotype and indirectly, through maternal hyperglycaemia, by the maternal genotype. This observation suggests that variation in fetal growth could be used in the assessment of the role of genes which modify either insulin secretion or insulin action.