Fetal Growth

Background Fully understanding the determinants and sequelae of fetal growth requires a continuous measure of birth weight adjusted for gestational age. Published United States reference data, however, provide estimates only of the median and lowest and highest 5th and 10th percentiles for birth weight at each gestational age. The purpose of our analysis was to create more continuous reference measures of birth weight for gestational age for use in epidemiologic analyses. Methods We used data from the most recent nationwide United States Natality datasets to generate multiple reference percentiles of birth weight at each completed week of gestation from 22 through 44 weeks. Gestational age was determined from last menstrual period. We analyzed data from 6,690,717 singleton infants with recorded birth weight and sex born to United States resident mothers in 1999 and 2000. Results Birth weight rose with greater gestational age, with increasing slopes during the third trimester and a leveling off beyond 40 weeks. Boys had higher birth weights than girls, later born children higher weights than firstborns, and infants born to non-Hispanic white mothers higher birth weights than those born to non-Hispanic black mothers. These results correspond well with previously published estimates reporting limited percentiles. Conclusions Our method provides comprehensive reference values of birth weight at 22 through 44 completed weeks of gestation, derived from broadly based nationwide data. Other approaches require assumptions of normality or of a functional relationship between gestational age and birth weight, which may not be appropriate. These data should prove useful for researchers investigating the predictors and outcomes of altered fetal growth.

Epidemiological findings and experimental studies in animals have shown that individual tissues and whole organ systems can be programmed in utero during critical periods of development with adverse consequences for their function in later life. Detailed morphometric analyses of the data have shown that certain patterns of intrauterine growth, particularly growth retardation, can be related to specific postnatal outcomes. Since hormones regulate fetal growth and the development of individual fetal tissues, they have a central role in intrauterine programming. Hormones such as insulin, insulin-like growth factors, thyroxine and the glucocorticoids act as nutritional and maturational signals and adapt fetal development to prevailing intrauterine conditions, thereby maximizing the chances of survival both in utero and at birth. However, these adaptations may have long-term sequelae. Of the hormones known to control fetal development, it is the glucocorticoids that are most likely to ca...

To examine pregnancy outcomes in women age 40 or older. We used data from the California Health Information for Policy Project, which consists of linked records from the birth certificate and the hospital discharge record of both mother and newborn of all births that occurred in acute care civilian hospitals in California between January 1, 1992, and December 31, 1993. The study population consisted of all women who delivered at age 40 or over. The control population was women who delivered between age 20 and 29 years during this 2-year period. We reviewed gestational age at delivery, birth weight, mode and type of delivery, discharge summary and birth certificate demographics, birth outcome, pregnancy, and delivery data. Approximately 1,160,000 women delivered during the study period, and 24,032 (2%) of these women were age 40 or older. Of this latter group, 4777 (20%) were nulliparous. The cesarean delivery rate for nulliparous women in the study population was 47.0%, and the rate...

To examine the association of maternal hemoglobin during pregnancy with preterm birth and small for gestational age (SGA). We performed a retrospective cohort analysis of hemoglobin and birth outcome among 173,031 pregnant women who attended publicly funded health programs in ten states and delivered a liveborn infant at 26-42 weeks' gestation. We defined preterm as less than 37 weeks' gestation and SGA as less than the tenth percentile of a US fetal growth reference. Risk of preterm birth was increased in women with low hemoglobin level in the first and second trimester. The odds ratio (OR) for preterm birth with moderate-to-severe anemia during the first trimester (more than three standard deviations [SD] below reference median hemoglobin, equivalent to less than 95 g/L at 12 weeks' gestation) was 1.68 (95% confidence interval [CI] 1.29, 2. 21). Anemia was not associated with SGA. High hemoglobin level during the first and second trimester was associated with SGA but not preterm birth. The ORs for SGA in women with very high hemoglobin level during the first and second trimester (more than three SDs above reference median hemoglobin, equivalent to greater than 149 g/L at 12 weeks' gestation and greater than 144 g/L at 18 weeks') were 1.27 (95% CI 1.02, 1.58) and 1.79 (95% CI 1.49, 2.15), respectively. These data highlight the importance of considering anemia and high hemoglobin level as indicators for adverse pregnancy outcome. An elevated hemoglobin level (greater than 144 g/L) is an indicator for possible pregnancy complications associated with poor plasma volume expansion, and should not be mistaken for good iron status.

Hormones have an important role in the control of fetal growth. They act on both tissue accretion and differentiation and enable a precise and orderly pattern of growth to occur during late gestation. In part, their actions on growth may be mediated by other growth factors such as the insulin-like growth factors (IGFs). Insulin stimulates fetal growth by increasing the mitotic drive and nutrient availability for tissue accretion. It has little effect on tissue differentiation. In contrast, the main effects of cortisol in utero are on tissue differentiation and maturation. Cortisol appears to act directly on the cells to alter gene transcription or post-translational processing of the gene products. Cortisol may also initiate the transition from the fetal to the adult modes of growth regulation by inducing the switch from IGF-II to IGF-I gene expression in the fetal liver. Thyroxine affects both tissue accretion and differentiation in the fetus by a combination of metabolic and non-m...

Maternal overweight and obesity in preg- nancy often result in fetal overgrowth, which increases the risk for the baby to develop metabolic syndrome later in life. However, the mechanisms underlying fetal overgrowth are not established. We developed a mouse model and hypothesized that a maternal high-fat (HF) diet causes up-regulation of placental nutrient trans- port, resulting in fetal overgrowth. C57BL/6J

Restricted fetal growth is associated with increased risk for the future development of Type 2 diabetes in humans. The study aim was to assess the glucose tolerance of old (seventeen months) male rats, which were growth restricted in early life due to maternal protein restriction during gestation and lactation. Rat mothers were fed diets containing either 20% or 8% protein and all offspring weaned onto a standard rat diet. In old-age fasting plasma glucose concentrations were significantly higher in the low protein offspring: 8.4 (1.3) mmol/l v. 5.3 (1.3) mmol/l (p = 0.005). Areas under the curves were increased by 67% for glucose (p = 0.01) and 81% for insulin (p = 0.01) in these rats in intravenous glucose tolerance tests, suggesting (a degree of) insulin resistance. These results show that early growth retardation due to maternal protein restriction leads to the development of diabetes in old male rat offspring. The diabetes is predominantly associated with insulin resistance.

Atenolol use may be associated with growth retardation when given in pregnancy, although the relationship to trimester of initiation, duration of treatment, and its use as monotherapy is still uncertain. To compare the obstetric and fetal outcome between women receiving atenolol (as monotherapy) and other antihypertensive drug monotherapies, and also to investigate the effect of duration of treatment on fetal growth, we performed a retrospective cohort study of 312 pregnancies in 223 women attending an Antenatal Hypertension Clinic. Atenolol (as monotherapy) was given in 78 pregnancies (25.0%), other types of antihypertensive drugs as monotherapy were given in 53 pregnancies (17.0%), and multiple drug combinations were given in 90 pregnancies (28.8%). In 91 pregnancies (29.2%) no antihypertensive drugs were given. Atenolol was found to be associated with lower birth weight and ponderal index values, with a trend toward a higher prevalence of preterm (<37 weeks) delivery and small...

Intrauterine growth restriction (IUGR) is a significant cause of infant mortality and morbidity. It is now clear that IUGR infants exhibit higher rates of coronary heart disease, type 2-diabetes, hypertension and stroke as adults. Therefore, fetal growth not only impacts the outcome of the perinatal period, but also impacts adult well-being. The etiologies of IUGR are numerous, but are often associated with abnormalities in placental structure and function. The process of implantation and placentation requires the production of a plethora of growth factors, cell-adhesion molecules, extracellular matrix proteins, hormones and transcription factors. Many of these exhibit altered expression within the placenta of IUGR pregnancies. However, it has been difficult to fully assess their role during the development of placental insufficiency (PI) in the human, underscoring the need for animal models. Using an ovine model of PI-IUGR we have observed changes in the expression of vascular endo...