Evidence of genetic regulation of fetal longitudinal growth

BACKGROUND: Genetic as well as environmental factors are important determinants of fetal growth but there have been few studies of the influence of paternal factors on fetal growth. AIM: To study the influence of paternal anthropometry on detailed measurements of offspring at birth. DESIGN: A prospective cohort study involving biochemistry, and anthropometry, of mothers and fathers at 28 weeks gestation, and detailed anthropometry of children within 24 h of birth. SUBJECTS: 567 White Caucasian singleton, non-diabetic, full term pregnancies recruited from central Exeter, UK. RESULTS: Paternal height, but not paternal BMI, was correlated with birth weight (r = 0.19) and with birth length (r = 0.33). This was independent of potential confounders and maternal height. All measurements of fetal skeletal growth including crown-rump, knee-heel and head circumference were associated with paternal height. Maternal height showed similar correlations with birth weight (r = 0.18) and birth length (r = 0.26). Maternal BMI was correlated with birth weight (r = 0.27) and birth length (r = 0.15). In a multifactorial analysis 38% of the variance in fetal height could be explained by gestation, sex, paternal height, maternal height, maternal glucose, maternal BMI, parity and maternal smoking. CONCLUSION: Paternal height has an independent influence on size at birth. This predominantly influences length and skeletal growth of the baby. In contrast to maternal obesity the degree of paternal obesity does not influence birth weight. This work suggests that there is genetic regulation of skeletal growth while the maternal environment predominantly alters the adiposity of the fetus.     

Effect of gestational age upon prealbumin and retinol binding protein in preterm and term infants

The relationships between maternal and umbilical cord levels of prealbumin and retinol binding protein (RBP) were studied in 68 mothers and in their appropriate-for-gestational-age neonates delivered between 25 and 42 weeks gestation. Arterial and venous concentrations of prealbumin and RBP in cord sera were also studied in a subsample of eight infants. In cord sera, prealbumin and RBP levels increased with gestational age (prealbumin, r = 0.47; RBP, r = 0.40, p less than 0.01), and were significantly different in neonates born at term compared to those born prematurely (mean +/- SD, prealbumin 12.0 +/- 3.9 mg/dl vs. 8.8 +/- 2.3 mg/dl, p less than 0.001; RBP, 2.3 +/- 0.8 vs. 1.8 +/- 0.5 mg/dl, p less than 0.005). No significant differences between arterial and venous concentrations of prealbumin and RBP were observed in cord blood. In maternal blood, serum prealbumin and RBP concentrations did not increase with length of gestation (25-42 weeks). Maternal prealbumin was not correlated significantly with infants' cord serum levels; the correlation coefficient for RBP was 0.29, p less than 0.05. Maternal prealbumin and RBP serum levels were approximately twice the values seen in neonates born both at term and prematurely. Although the difference between premature and full-term cord levels of prealbumin and RBP may reflect an increase in hepatic protein synthesis that occurs with maturation of the fetus and/or a change in placental function after 37 weeks gestation, neither of these factors sufficiently explains the variance in neonatal prealbumin and RBP levels.     

Gender difference in cord serum ferritin concentrations.

We measured cord serum ferritin concentrations in a total of 255 infants (116 females and 139 males), and evaluated the association between these values and various neonatal as well as maternal characteristics. The mean ferritin concentration in females (166 +/- 110 microg/l) was significantly higher than that in male infants (123 +/- 77 microg/l). The gender differences in ferritin were significant within groups of infants with fetal growth restriction, those who weighed <3,000 g, those whose mothers were African Americans or <25 years old. Maternal serum ferritin concentrations at 36 weeks of gestation significantly correlated with cord serum ferritin of male infants (r = 0.32, p < 0.001), whereas the association was not significant for females (r = 0.09, p > 0.41). Although the mechanism of the gender difference is unknown, it may be important to consider the sex of neonates when evaluating their iron nutriture immediately after birth.     

Anthropometry of fetal growth in rural Malawi in relation to maternal malaria and HIV status

OBJECTIVE: To describe fetal growth centiles in relation to maternal malaria and HIV status, using cross sectional measurements at birth. DESIGN: A cross sectional study of pregnant women and their babies. Data on maternal socioeconomic status and current pregnancy, including HIV status and newborn anthropometry, were collected. Malaria parasitaemia was assessed in maternal peripheral and placental blood, fetal haemoglobin was measured in cord blood, and maternal HIV status was determined. SETTING: Two district hospitals in rural southern Malawi, between March 1993 and July 1994. OUTCOME VARIABLES: Newborn weight, length, Rohrer's ponderal index. RESULTS: Maternal HIV (adjusted odds ratio (AOR) 1.76 (95% confidence interval 1.04 to 2.98)) and first pregnancy (AOR 1.83 (1.10 to 3.05)) were independently associated with low weight for age. Placental or peripheral parasitaemia at delivery (AOR 1.73 (1.02 to 2.88)) and primigravidae (AOR 2.13 (1.27 to 3.59)) were independently associated with low length for age. Maternal malaria at delivery and primiparity were associated with reduced newborn weight and length but not with disproportionate growth. Maternal HIV infection was associated only with reduced birth weight. The malaria and parity effect occurred throughout gestational weeks 30-40, but the HIV effect primarily after 38 weeks gestation. CONCLUSION: Fetal growth retardation in weight and length commonly occurs in this highly malarious area and is present from 30 weeks gestation. A maternal HIV effect on fetal weight occurred after 38 weeks gestation.     

Influence of gestational age and intrauterine growth on leptin concentrations in venous cord blood of human newborns

BACKGROUND: The ob gene product leptin is involved in the regulation of body weight and energy expenditure, suggesting a potential role of leptin in embryonal and fetal development and progression of pregnancy. In term infants, leptin concentrations showed a positive correlation with birth weight. We aimed at comparing leptin cord blood levels in AGA (appropriate for gestational age) to SGA (small for gestational age) preterm and term newborns. PATIENTS AND METHODS: Ninety-seven human newborns, 47 females and 50 males, 33 born at term and 64 born before 36 weeks of gestation, were studied prospectively. Leptin concentrations in venous cord blood were determined using a specific RIA (radioimmunoassay). RESULTS: In term newborns, mean gestational age (GA) was 39 weeks (wk) (+/- 0.7 wk) and mean birth weight (BW) was 3316 g (+/- 473 g); in preterm newborns (n = 64), mean GA was 30 wk (+/- 5.0 wk) and mean BW was 1398 g (+/- 505 g). Mean standard deviation score of birth weight (BW SDS) was calculated as - 0.47. Mean leptin concentrations in term newborns differed significantly from those in preterm newborns (9.21 +/- 2.63 ng/ml vs. 1.58 +/- 0.88 ng/ml; p < 0.0001). In preterm and term infants, leptin concentrations showed a linear correlation with BW (r = 0.46; p < 0.0001) and GA (r = 0.48; p < 0.0001), respectively. Leptin levels were best predicted by an exponential regression model with GA (Leptin = exp(- 4.41 + 0.14 x GA); r = 0.61; p < 0.0001). Using multivariate regression analysis (r = 0.57; p < 0.0001), we found significant influences of GA (p < 0.00001) and BW SDS (p < 0.05) on leptin levels. No difference was observed between leptin values in AGA versus SGA preterm infants. CONCLUSION: These data suggest fetal leptin levels to be primarily determined by GA and additionally modulated by growth restriction in term newborns. We found a dramatic increase at weeks 33 to 35 of gestation and no modulation by BW SDS in very preterm infants.     

Perinatal bone turnover in term human neonates and the influence of maternal smoking

Bone turnover in neonates appears independently of the comparably low maternal bone turnover, but there is only sparse information on the effect of the in utero environment on fetal bone turnover. Postnatally, the resuming growth velocity and alterations in mineral homeostasis affect neonatal bone turnover. This study evaluated the relationship of bone marker concentrations to maternal and fetal auxological variables as well as maternal smoking and assessed the short-term change in bone markers during the first days of life. Serum markers of bone formation [osteocalcin and bone-specific alkaline phosphatase (BALP)] and bone resorption (C-terminal telopeptide of type I collagen) were measured in cord blood and at discharge (median d 3) in 69 healthy term neonates. Concentrations of BALP were significantly lower in neonates of smokers (n = 16) compared with nonsmokers (n = 53), both at birth (p = 0.013) and at discharge (p = 0.036). Both cord osteocalcin and BALP were negatively related to maternal weight and maternal body mass index. Maternal smoking and pregnancy weight gain were the predictors of cord BALP (r2 = 0.24; p < 0.001), whereas the mode of delivery best predicted cord C-terminal telopeptide of type I collagen levels (r2 = 0.19; p < 0.001). C-terminal telopeptide of type I collagen and osteocalcin increased significantly (p < 0.001) from birth to discharge, whereas BALP levels did not change significantly during the same period. Our results suggest that maternal smoking during pregnancy and maternal obesity may have a negative impact on fetal bone formation. The significant increase of osteocalcin and C-terminal telopeptide of type I collagen may result either from an increase in bone turnover or altered renal clearance.     

Fetal intravenous nutritional supplementation ameliorates the development of embolization-induced growth retardation in sheep

Since decreased transfer of nutrients into the fetus has been documented in many forms of intrauterine growth retardation, we evaluated whether increasing fetal nutrient availability would prevent the development of experimental growth retardation in fetal lambs. Fetuses were separated into three groups: E, animals growth retarded by repetitive uteroplacental embolization (n = 8); ES, animals treated as in E and given fetal femoral venous infusions of 5% glucose and 6.8% amino acids (n = 7); and C, controls (n = 8). The duration and density of embolization were the same in E and ES; initial physical and metabolic characteristics and gestation at delivery were similar in all groups. E birth weight was reduced 26% compared to C (2888 +/- 373 SEM g versus 3880 +/- 277 g, p less than 0.05); fetal/maternal weight ratio was decreased 35% (p less than 0.005) and ponderal index decreased 22% (p less than 0.005). Asymmetric growth retardation was indicated in E by an increased brain/body weight ratio (p less than 0.05). ES fetuses, in contrast, showed no differences from C in birth weight (3601 +/- 190 g) or body proportions. ES were larger than E, with a greater fetal/maternal weight ratio and ponderal index (p less than 0.05 for both). In E and ES, size at birth showed a positive relation to the amount of supplements received. The average daily supplementation rate correlated with the fetal/maternal weight ratio and with the ponderal index (for both r = 0.62, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Free erythrocyte protoporphyrin as an index of perinatal iron status

The relationship between free erythrocyte protoporphyrin and conventional indices of iron status was studied in 49 mothers and their infants. Maternal venous blood samples were collected at 34 weeks gestation and at delivery. The corresponding infant blood samples were collected from the umbilical cord and at age 6 weeks. In each case free erythrocyte protoporphyrin, serum iron, total iron binding capacity, and serum ferritin were determined. Cord free erythrocyte protoporphyrin was negatively correlated with maternal ferritin at 34 weeks gestation (p = 0.016) and at delivery (p = 0.014), and with transferrin saturation at delivery (p = 0.026). The infants' haemoglobin concentrations at 6 weeks were significantly negatively related to maternal free erythrocyte protoporphyrin at 34 weeks (p = 0.026) and at delivery (p = 0.026). Cord free erythrocyte protoporphyrin is an index of maternal iron status in the last trimester. Maternal free erythrocyte protoporphyrin in the last trimester predicts the magnitude of physiological anaemia of the infant at age 6 weeks.     

Leptin,fetal growth and insulin resistance in non-diabetic pregnancies

Background

Interrogation of the association between leptin, insulin resistance and fetal growth may provide a biological link for the fetal programming of later metabolic health.

Aims

Our aim was to clarify the relationship between maternal and fetal leptin, insulin resistance and fetal growth.

Study design

Maternal leptin, glucose and insulin were measured in early pregnancy and at 28 weeks and the HOMA index calculated. At 34 weeks, ultrasound scan assessed fetal weight and adiposity (abdominal wall width). At delivery birthweight was recorded and cord blood analyzed for fetal c-peptide and leptin. Analysis was performed using a multivariate linear regression model.

Subjects

574 non-diabetic pregnant women.

Outcome measures

Fetal growth and maternal and fetal insulin resistance.

Results

On multivariate analysis a relationship was identified between maternal and fetal leptin concentrations at each time point and maternal body mass index. Maternal leptin was related to insulin resistance in early pregnancy (β = 0.15, p = 0.02) and at 28 week gestation (β = 0.27, p < 0.001). Fetal insulin resistance correlated with maternal leptin in early pregnancy (β = 0.17, p = 0.004); at 28 weeks (β = 0.12, p = 0.05), and with leptin in cord blood (r = 0.28, p < 0.001).Fetal weight at 34 weeks was related to maternal leptin in early pregnancy (β = 0.16, p = 0.02). Both maternal and fetal leptin correlated with infant size at birth (β = 0.12, p = 0.07 in early pregnancy, β = 0.21, p = 0.004 in cord blood), independent of all other outcome measures.

Conclusion

Our findings have confirmed that in a non-diabetic cohort there is a link between maternal and fetal leptin and insulin resistance. We also established a link between maternal leptin in early pregnancy and both fetal and neonatal size. These results add to the growing body of evidence suggesting a role for leptin in the fetal programming of childhood obesity and metabolic dysfunction.     

Cord blood leptin levels: relationship to body weight, body mass index, sex and insulin and cortisol levels of maternal-newborn pairs at delivery

To investigate leptin and to which factors it is related during the perinatal period, we measured serum leptin levels of 46 mothers at delivery, umbilical cord blood and infants on the third day of life. Maternal leptin was higher than in cord (p < 0.001), and did not correlate with maternal age, body weight, body mass index, weight gain during pregnancy, serum glucose, cholesterol, triglycerides, CPE, cortisol or HbA1c levels, nor any biochemical values or anthropometric data of the newborns (p > 0.05). In cord blood, leptin was significantly higher than in 3 day-old infants (p < 0.05), and correlated only with maternal insulin and glucose (r = 0.5, p < 0.01 and r = 0.4, p < 0.05, respectively). In 3 day-old infants, leptin did not correlate with any clinical data (p > 0.05). Leptin was not different in the two sexes (p > 0.05). Serum leptin levels were not related to adiposity of the mother-infant pairs or neonatal growth, and were not different in the two sexes during the perinatal period.     

Tissue and serum concentrations of somatomedin-C/insulin-like growth factor I in fetal rats made growth retarded by uterine artery ligation

To study the role of somatomedin-C/insulin-like growth factor I (Sm-C/IGF I) in fetal growth, intrauterine growth retardation was induced by uterine artery ligation on day 17 of gestation in pregnant rats. Fetuses of the nonligated horns served as appropriately grown controls. On day 21 of gestation, fetal serum, liver, and lung were obtained and analyzed for Sm-C/IGF I by radioimmunoassay. Serum insulin was determined by radioimmunoassay and serum glucose by a glucose oxidase method. Fetal weight, serum concentrations of glucose, insulin and Sm-C/IGF I, and liver Sm-C/IGF I concentrations were reduced in fetuses from uterine artery ligated horns, as compared to those from nonligated control horns. Fetal weight was correlated with serum glucose (r = 0.703; p less than 0.001), liver Sm-C/IGF I (r = 0.682; p less than 0.001), and serum Sm-C/IGF I (r = 0.452; p less than 0.001). Stepwise linear regression demonstrated that these three factors in combination correlated highly with fetal weight (r = 0.836). No correlation was found for serum insulin or lung Sm-C/IGF I and fetal weight. Serum insulin concentrations correlated with serum, but not liver, Sm-C/IGF I concentrations, making a direct effect of insulin on Sm-C/IGF I synthesis appear unlikely. However, serum glucose concentrations correlated with liver (r = 0.404; p less than 0.001) and with serum Sm-C/IGF I (r = 0.308; p less than 0.002) concentrations, implicating fetal glucose delivery in the regulation of Sm-C/IGF I synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal and paternal height and BMI and patterns of fetal growth: The Pune Maternal Nutrition Study

We examined the differential associations of each parent's height and BMI with fetal growth, and examined the pattern of the associations through gestation. Data are from 557 term pregnancies in the Pune Maternal Nutrition Study. Size and conditional growth outcomes from 17 to 29 weeks to birth were derived from ultrasound and birth measures of head circumference, abdominal circumference, femur length and placental volume (at 17 weeks only). Parental height was positively associated with fetal head circumference and femur length. The associations with paternal height were detectible earlier in gestation (17-29 weeks) compared to the associations with maternal height. Fetuses of mothers with a higher BMI had a smaller mean head circumference at 17 weeks, but caught up to have larger head circumference at birth. Maternal but not paternal BMI, and paternal but not maternal height, were positively associated with placental volume. The opposing associations of placenta and fetal head growth with maternal BMI at 17 weeks could indicate prioritisation of early placental development, possibly as a strategy to facilitate growth in late gestation. This study has highlighted how the pattern of parental-fetal associations varies over gestation. Further follow-up will determine whether and how these variations in fetal/placental development relate to health in later life.     

Familial, anthropometric, and metabolic associations of intramyocellular lipid levels in prepubertal males.

The cause of skeletal muscle insulin resistance is unclear, but high levels of intramyocellular lipids are often present in affected individuals. We aimed to establish the metabolic, familial, and anthropometric associations of intramyocellular lipid in a pediatric population. We studied 41 boys aged 6.9-9.9 y and 23 of their mothers by proton magnetic resonance spectroscopy. We related muscle lipid levels to important factors that define an increased risk of developing insulin resistance in adult life. There were significant associations between the boys' intramyocellular lipid and their waist circumference (r = 0.42, p = 0.007), body mass index SD score (r = 0.32, p = 0.04), weight SD score (r = 0.32, p = 0.04), glucose:insulin ratio (r= -0.59, p = 0.04), maternal log fasting insulin levels (r = 0.44, p = 0.04), maternal body mass index (r = 0.46, p = 0.03), and maternal intramyocellular lipid (r = 0.62, p = 0.003). In the 41 boys, waist circumference explained 19% of the variance in the boys' intramyocellular lipid. Maternal intramyocellular lipid explained 39% of the variance in the boys' intramyocellular lipid in the sub-group of 23 boys. Intramyocellular lipid levels have both metabolic and anthropometric associations in childhood. Before puberty, children develop or inherit muscle metabolic characteristics that are associated both with insulin resistance and risk factors for the development of insulin resistance syndrome in adult life.     

Maternal anxiety in late pregnancy: effect on fetal movements and fetal heart rate

AIM: To determine whether maternal state and trait anxiety levels affect fetal movements or fetal heart rate (FHR) in the third trimester. SUBJECTS: Forty-one healthy pregnant nulliparous women not on medication and with a singleton pregnancy. STUDY DESIGN: Maternal anxiety was assessed using the Spielberger State- Trait Anxiety Inventory (Form Y) at 36 gestational weeks. The fetuses of the women were examined at 37-40 gestational weeks with ultrasound observation of fetal movements and cardiotocography (CTG). The results of the fetal examinations were compared between women with low and high anxiety scores (low scores being defined as scores below the median and high scores as scores equal to or above the median of the study population), and correlation analyses between anxiety scores and the outcome variables were performed. OUTCOME MEASURES: The presence and duration (expressed as a percentage of the total examination time) of FHR patterns A, B, C, and D, the percentage duration of fetal movements in each FHR pattern, baseline FHR and FHR variability in each FHR pattern. RESULTS: The presence of FHR patterns A, B, C, and D, the duration of FHR patterns A, B, and C, FHR variability in FHR patterns A, B, and C, baseline FHR and the percentage duration of fetal movements in each FHR pattern did not differ between women with low and high state and trait anxiety scores. In fetuses with FHR pattern D, the duration of FHR pattern D increased with increasing maternal trait anxiety scores, (rho=0.88; p=0.008), and FHR variability in FHR pattern D increased with maternal state and trait anxiety scores (r=0.86, p=0.01; r=0.96, p=0.001). CONCLUSION: Maternal anxiety does not seem to affect fetal movements or baseline FHR in late pregnancy, but there is a possible association between maternal anxiety and the duration of FHR pattern D and FHR variability in FHR pattern D.     

Amylin peptide levels are raised in infants of diabetic mothers.

BACKGROUND: Amylin is a novel 37 amino acid peptide hormone that is co-secreted with insulin from the pancreas in response to food intake. As a potent inhibitor of gastric emptying it plays an important role in the control of carbohydrate absorption. Feed intolerance is common in infants of diabetic mothers (IDM). AIMS: To establish a normal range of amylin levels in healthy neonates, and to determine whether serum amylin levels are raised in IDM. METHODS: A serial sample of 221 infants > or =28 weeks gestation was enrolled prior to delivery over a 12 month period. Blood samples collected immediately after birth (umbilical cord), and at the routine Guthrie test were analysed for amylin and insulin levels. RESULTS: Amylin levels in umbilical cord (n = 181) and Guthrie samples (n = 33) of healthy infants were 5.7 (3.0-9.1) and 6.9 (2.9-9.0) pmol/l respectively. IDM had significantly raised amylin levels in both cord (n = 31; 32.7 pmol/l, 25.9-48.1) and Guthrie samples (n = 8; 18.1 pmol/l, 15.3-23.6). Amylin correlated positively with insulin (n = 42; r = 0.67; 95% CI 0.4 to 0.81), birth weight (r = 0.22; 95% CI 0.08 to 0.36), and gestation (r = 0.18; 95% CI 0.03 to 0.32). Umbilical cord venous amylin levels showed agreement with arterial cord amylin levels (n = 34, mean bias -0.2, 95% CI 3.1 to -3.6). CONCLUSIONS: Amylin levels are significantly increased in the umbilical cord and Guthrie blood samples in IDM.     

Human fetal and maternal corticotrophin releasing hormone responses to acute stress

OBJECTIVES: To study the effect of acute stress, caused by intrauterine needling at the intrahepatic vein (IHV), on fetal plasma concentrations of corticotrophin releasing hormone (CRH), and to compare paired fetal and maternal samples for CRH concentration to determine the extent of their joint control. DESIGN: Venous blood samples were obtained from fetuses (gestational age 17-38 weeks) undergoing fetal blood sampling (n = 29) or intrauterine transfusion (n = 17) through either the IHV or the placental cord insertion (PCI). SETTING: The Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London, UK. PATIENTS: Pregnant women undergoing clinically indicated fetal blood sampling or intrauterine blood/platelet transfusion. RESULTS: Fetal plasma cortisol increased with intrahepatic vein transfusion (mean (SD) cortisol response Delta64.7 (54.5) nmol/l; p < 0.0001, n = 11), and fetal corticotrophin concentrations were higher after IHV (n = 7) than PCI needling (n = 6). Neither fetal nor maternal plasma CRH increased after IHV transfusion. Fetal CRH levels did not rise with gestation, whereas maternal CRH levels did (r = 0.58; n = 36; p < 0.0001). There was a modest correlation between paired maternal and fetal values (r = 0.36; n = 36; p = 0.03). CONCLUSIONS: Acute fetal stress, caused by IHV needling of the fetal abdomen, resulted in hypothalamic-pituitary-adrenal axis activation, as shown by a rise in fetal cortisol and corticotrophin. However, it did not result in measurable CRH release into fetal plasma. This suggests that fetal plasma CRH is not derived from the hypophyseal-portal circulation, but from another source, presumably the placenta.     

Risk factors for unexplained antepartum fetal death in Norway 1967-1998

OBJECTIVE: To relate unexplained antepartum fetal death with maternal and fetal characteristics in order to identify risk factors. DESIGN: Population-based study based on records of 1,676,160 singleton births with gestational age > or =28 weeks. Unexplained antepartum fetal death was defined as fetal death before labour without known fetal, placental, or maternal pathology. RESULTS: Although unexplained fetal mortality in general declined from 2.4 per 1000 births in 1967-1976 to 1.6 in 1977-1998, the proportion among all fetal deaths increased from 30% to 43% during the same period of observation. Unexplained fetal death occurred later in gestation than explained. From 39 weeks of gestation, the risk increased progressively to 50/10,000 in women aged > or =35 years and <10/10,000 in women <25 years. In birth order > or =5, the risk was particularly high after 39 weeks of gestation. For birth weight percentile 2.5-9.9 and > or =97.5, unexplained fetal death was four and three times more likely to occur, respectively. We found an additive effect of maternal age and birth weight percentile 2.5-9.9. Women with less than 10 years education had higher risk than women with 13 years or more (OR=1.6). Weaker associations were observed with female gender, unmarried mothers, and winter season. CONCLUSIONS: Unexplained antepartum fetal death occurred later in gestation than explained and was associated with high maternal age, multiparity, low education, and moderately low and high birth weight percentile. The increased risk in post-term pregnancies and the additive effect of maternal age and birth weight percentile 2.5-9.9 suggests that older women would benefit from monitoring of fetal growth.     

孕期膳食血糖生成指数变化与出生体重及母子胰岛素抵抗水平的关系

目的：探讨超重孕妇孕期膳食血糖生成指数（GI）变化水平与新生儿出生体重及母子胰岛素抵抗水平的关系。方法：选择在江苏省昆山市妇幼保健所及上海市国际和平妇幼保健院参加产检的超重孕妇为研究对象。前瞻性收集孕妇初次产检及孕中期膳食资料,计算GI变化水平（ΔGI）。采用Pearson相关分析ΔGI与新生儿出生体重、孕晚期空腹胰岛素及脐血C肽之间的相关关系,利用多元回归校正混杂因素的影响,进一步分析ΔGI与三者之间的关系。将ΔGI分为4组（<25%、~50%、~75%和＞75%）, 出生体重分为巨大儿、正常体重儿、低出生体重儿3组,应用有序多分类Logistic 回归分析孕期ΔGI和出生体重各分组之间的关系。结果：本文共纳入392名超重孕妇,初诊和孕中期膳食GI平均水平分别为64.4±9.2和63.8±9.5,ΔGI为-0.6±12.7。孕晚期空腹胰岛素平均水平为11.6(7.4~15.8) μU·mL-1。新生儿平均出生体重（3489.7±519.6）g,巨大儿发生率14.4%,脐血C肽的平均水平为0.7(0.4~1.0) ng·mL-1。相关分析并未发现ΔGI与新生儿出生体重、孕晚期空腹胰岛素及脐血C肽之间的关系。多元线性逐步回归分析显示新生儿出生体重与ΔGI、孕期增重、新生儿性别、分娩孕周有关。有序多分类Logistic 回归分析显示,随着孕期ΔGI的增加,新生儿出生体重呈上升趋势（OR=1.54,95% CI:1.06~2.25）。多元回归分析并未发现ΔGI与孕晚期空腹胰岛素、脐血C肽之间的关系。结论：超重孕妇孕期膳食GI变化水平与新生儿出生体重显著相关,与母子胰岛素抵抗水平无关。     

Fetal leptin influences birth weight in twins with discordant growth

The objective of this study was to determine the plasma leptin concentrations in twin pregnancies in relation to chorionicity and discordant fetal growth. We studied 53 twin pregnancies of which 26 had growth discordance of > or =20% and 27 were concordant for growth (discordance of < or =10%). Paired maternal and fetal blood samples were obtained at birth. Plasma leptin concentrations were measured by RIA. In discordant monochorionic pregnancies, fetal plasma leptin concentrations in the intrauterine growth-restricted twins were lower than the co-twins with normal growth (mean difference, 3 ng/mL; 95% CI, 2.2 to 3.3 ng/mL; p < 0.001), whereas no such differences were present between concordant monochorionic twin pairs (mean difference, 0.1 ng/mL; 95% CI, -0.2 to 0.5 ng/mL; NS). Similarly, fetal plasma leptin concentrations in appropriate-for-gestational-age twins were higher than in the intrauterine growth-restricted twins of the discordant dichorionic pregnancies (mean difference, 2.4 ng/mL; 95% CI, 1.8 to 3.1 ng/mL; p < 0.001). No such differences were present between the concordant dichorionic twin pairs (mean difference, 0.2 ng/mL; 95% CI, -0.1 to 0.5 ng/mL; NS). Maternal plasma leptin concentrations were comparable among all four groups and were higher than the fetal levels. Fetal plasma leptin concentrations of the intrauterine growth-restricted twins of discordant monochorionic and dichorionic pregnancies were comparable. There was a positive association between cord plasma leptin concentrations and the birth weight of twin pairs (y = 0.002x - 0.32; r = 0.63; p < 0.001; n = 106). A significant positive association was also found between percent differences in birth weight and fetal delta plasma leptin concentrations of the discordant monochorionic and dichorionic twin pairs (y = 0.057x + 0.93; r = 0.60; p < 0.001, n = 26). In conclusion, irrespective of chorionicity, plasma leptin concentrations in intrauterine growth-restricted twins were 2-fold lower than their co-twins with normal growth. These differences may be attributed to placental factors.     

Influence of maternal diabetes mellitus on fetal iron status

OBJECTIVE: To determine the effects of maternal diabetes on fetal iron status using serum transferrin receptors (STfR) and their ratio to ferritin (TfR-F index) in cord blood. METHODS: Iron, ferritin, erythropoietin, STfR and haemoglobin concentration were measured and TfR-F index calculated in 97 maternal/cord blood pairs. Forty-nine women had type 1 diabetes (diagnosed before pregnancy) and these were compared with forty-eight non- diabetic controls. The women with type 1 diabetes were recruited consecutively from attendance at the joint antenatal endocrine clinic while the control group of women was recruited from consecutive attendance at the remaining antenatal clinics. RESULTS: The infants of the diabetic women had significantly lower levels of ferritin (47 vs 169 mug/l; p<0.01) and higher STfR (17.4 vs 12.9 mg/l; p<0.01) and TfR-F index (10.4 vs 5.8; p<0.01) than controls. They were also significantly more acidotic at birth (7.25 vs 7.30; p<0.01), were born at an earlier gestation (36.7 vs 39.7 weeks; p<0.01) and had higher z Scores for weight (0.53 vs 0.02; p = 0.016). CONCLUSIONS: Maternal diabetes causes depletion of fetal iron stores and is associated with higher fetal iron demands as indicated by higher STfR level and TfR-F index in cord blood.