Fetal serum levels of insulin,growth hormone and insulin-like growth factor-I in concordant and discordant twin gestations

Objective: To examine the role of insulin, growth hormone and insulin-like growth factor (IGF)-I in concordant and discordant twin pairs. Methods: Umbilical cord serum samples were obtained from 20 twin pairs with weight discordancy (intertwin birth weight difference > 20%) and from 20 concordant twins (intertwin birth weight difference < 20%), both groups of similar gestational age, gravidity, and parity. The serum samples were analyzed for the levels of IGF-I, growth hormone and insulin in both maternal and fetal compartments. Results: Among the group of discordant twins, the normally grown twin, in all cases, had significantly higher cord serum IGF-I levels than their growth-restricted co-twin (108 &#45 73 ng/ml vs. 39 &#45 24 ng/ml; p < 0.01). There were no significant intertwin differences in the cord blood IGF-I levels in the concordant twin pairs (87 &#45 44 vs. 88 &#45 48 ng/ml; p = 0.986). Insulin and growth hormone levels did not correlate with intertwin birth weight differences. Conclusion: These data demonstrate that IGF-I is important in the regulation of both normal and restricted fetal growth in utero, and its action appears to be, at least in part, through an endocrine action. The precise role of growth hormone and insulin in fetal growth restriction remains uncertain.     

Placental transport rather than maternal concentration of amino acids regulates fetal growth in monochorionic twins: implications for fetal origin hypothesis.

OBJECTIVE: The cause of discordant growth in monochorionic twins is not clear. We hypothesize that growth restriction of 1 monochorionic twin is due to fetal under-nutrition. STUDY DESIGN: We measured plasma amino acid concentrations by high performance liquid chromatography in maternal venous and fetal umbilical cord venous blood samples that were collected at birth from gestational age-matched monochorionic twins (n = 14) with a birth weight discordance of > or =20%. The concordant monochorionic twins with birth weight differences of < or =10% constitute a control group. RESULTS: In the intrauterine growth-restricted twins, fetal concentrations of essential amino acids valine (P <.01), leucine (P <.01), isoleucine (P <.01), phenylalanine (P <.01), and L-arginine (P <.05) were lower than the co-twins and concordant monochorionic twin pairs. Fetal concentrations of the nonessential amino acids taurine (P <.001), serine (P <.01), glycine (P <.01), tyrosine (P <.01), and aspartic acid (P <.01) were lower in the intrauterine growth-restricted twin than the co-twin or concordant monochorionic twins. No such differences were found between concordant monochorionic twin pairs. Maternal amino acid concentrations were similar between discordant and concordant groups. CONCLUSION: Concentrations of certain essential and nonessential amino acids in the intrauterine growth-restricted twins were lower than the co-twins. These differences support the hypothesis that intrauterine growth-restriction that affects 1 of the monochorionic twins is due to the impaired placental transport of amino acids rather than intertwin transfusion of blood.     

Ghrelin levels in cord blood from concordant and discordant twin pairs: association with birth weight and postnatal catch-up growth

Objective.?To determine whether cord blood ghrelin levels in discordant and concordant twins predict postnatal catch-up growth.

Methods.?After obtaining parental consent, cord blood samples were collected at delivery for total ghrelin analysis. Infant weight, length and head circumference were obtained at birth, 2, 4, and 6 months of age. Data points post-discharge were obtained from the pediatrician's office or via parent contact. Pearson correlation evaluated the relationship between cord blood ghrelin levels and postnatal catch-up growth.

Results.?There was a statistically significant correlation between cord blood ghrelin levels and birth weight among concordant twins, but not among the discordant twins. Cord blood ghrelin levels did not predict postnatal growth at 6 months of age overall, but did so in the subset of monochorionic, discordant pairs.

Conclusion.?Cord blood ghrelin levels did not correlate overall with birth size or postnatal catch-up growth in concordant and discordant twin pairs, but did so in selected subsets. Further studies are needed.     

Angiogenic growth factors in maternal and fetal serum in concordant and discordant twin pregnancies

Abstract

Objective: To assess soluble fms-like tyrosin kinase 1 (sFlt-1), free vascular endothelial growth factor (f-VEGF) and the f-VEGF/sFlt-1 quotient in twin pregnancies, and to determine if they are impaired in discordant twins.

Methods: Case-control study between 18 discordant and 46 concordant twin pregnancies. Angiogenic growth factors were measured in maternal serum during pregnancy and in umbilical artery and vein at birth.

Results: Discordant twins were more often conceived by assisted reproductive techniques than concordant twins. Maternal plasma f-VEGF was significantly lower in discordant twins (p?=?0.04). F-VEGF and f-VEGF/sFlt-1 in the whole sample show a significant higher level in concordant twins. When we analyzed umbilical cord angiogenic factors, the smaller twin had a lower f-VEGF/sFlt-1 quotient (p?=?0.01). We found no correlations between maternal or umbilical growth factors and placental or fetal weight. No difference was found in veno-arterial levels of angiogenic factors in each twin; however, there was a significant rise in arterial f-VEGF (p?=?0.06) in discordant twins.

Conclusion: Mothers of discordant twins have a more anti-angiogenic environment compared to those of concordant twins. We also found an anti-angiogenic environment in the small twin when we compared umbilical vein angiogenic factors against its big co-twin.     

Intertwin birth weight discordance as a potential adaptive measure to promote gestational age

OBJECTIVE: To determine if discordant twins are delivered at a more advanced gestational age than concordant twins of the same total twin birth weight. STUDY DESIGN: We used the U.S. National Center for Health Statistics matched multiple birth data file containing all twin births in the United States from 1995 through 1997. Birth weight discordance was defined as > 25% difference between the heavier and lighter twin. We compared mean gestational age between concordant and discordant pairs at 250-g total birth weight intervals in the entire population and in the subgroups of primiparas and multiparas. RESULTS: The frequency of discordant pairs declined with increasing total twin birth weight, from 7.2% at 3,000-3,250 g, to 3% at 4,750-5,000 g (R2 = .94, P < .05), with no significant difference between primiparas and multiparas (all P values > .05). The mean gestational age of discordant pairs was significantly higher across the entire range of total birth weight intervals except for the uppermost interval (> 4,750 g). The effect of discordance on gestational age was modified by parity, with significant differences between concordant and discordant pairs among primiparas mainly at the lower birth weight strata (P < .05). CONCLUSION: In the total twin birth weight range of 3,000-5,000 g, birth weight discordant twins are delivered at a more advanced gestational age than concordant twins. Discordant growth may serve as an adaptive measure to promote maturity by reducing the inevitable uterine overdistension.     

Fetal biometric parameters, twin type and birth weight difference. A longitudinal study

OBJECTIVE: To examine the relationship between twin type, divided by zygosity, chorionicity, and birth weight difference [more or less than 15% intertwin weight difference at delivery] on fetal biometric measurements, including biparietal diameter, transverse abdominal diameter, head and abdominal circumferences (AC) and head and abdominal areas, femur length (FL), transverse cerebellar diameter, cerebellar circumference and cerebellar area at 18, 23, 28 and 32 weeks of gestational age. STUDY DESIGN: A prospective and longitudinal study was done on 75 twin pairs that did not present the twin-twin transfusion syndrome (150 fetuses) divided into birth weight difference group I (<15%) and group II (>/=15%). The twin pairs were divided into three groups: dizygotic, monochorionic, and dichorionic-monozygotic. In each group the differences in various ultrasound indices were evaluated in reference to discordant growth or concordant growth. RESULTS: In our sample, there were no monozygotic twin pairs with dichorionic placentation with a birth weight difference of more than 15%. Significant associations of group and gestational age were found in dizygotic and monochorionic twins. Intrapair differences were significantly higher in group II (>/=15%) than in group I (<15%) for all fetal parameters studied except for AC, abdominal area and all cerebellar parameters. The value of these discrepancies increased according to gestational age except for FL. Significant interactions between group and zygosity type indicated that intrapair FL differences were more associated with group in monochorionic twins, whereas intrapair transverse cerebellar diameter differences were more associated with group in dizygotic twins. CONCLUSION: Our data show that most fetal biometric parameters are associated with birth weight discordancy. Abdominal area could be a relevant marker for twins with obstetric complications. Note that this is the first research that has studied a twin sample divided by both twin type and birth weight group.     

Sonographic prediction of significant intertwin birth weight discordance

OBJECT: To evaluate the usefulness of sonographic prediction of significant birth weight discordance in twin pregnancies. STUDY DESIGN: Included in the study were live twin pairs with a gestational age of 24 weeks at birth who had received a sonographic examination within 28 days of delivery. Correlation tests and ROC curves were used to evaluate the predictability of significant intertwin growth discordance. RESULTS: A total of 575 twin pregnancies were included in the study. The estimated discordance by sonographic examination proved to be an effective predictor of discordant twin growth. The birth weight discordance estimated by sonography tended to underestimate the degree of discordant twins. CONCLUSION: If a sonographic examination is done within 28 days of delivery, it is a reliable predictor of twin birth weight discordance at the following levels: 15%, 20%, 25% or 30%. In order to obtain a higher sensitivity, the cut-off value of estimated birth weight discordance needs to be decreased by 5%.     

胰岛素样生长因子及胰岛素样生长因子结合蛋白-3与胎儿生长受限的关系

目的　探讨胰岛素样生长因子 (IGF) Ⅰ、IGF Ⅱ和IGF结合蛋白 3(IGFBP 3)与胎儿生长的关系 ,以及IGF在胎儿生长受限 (FGR)发病中的作用。方法　选取 2 0例分娩FGR胎儿 (FGR组 )、10例分娩巨大儿 (巨大儿组 )及 2 0例分娩正常儿 (对照组 )的产妇 ,抽取 3组产妇分娩后肘静脉血及其新生儿脐静脉血 ,分离血清。采用放射免疫法和免疫放射法测定 3组产妇及其新生儿血清中IGF Ⅰ、IGF Ⅱ及IGFBP 3的水平。结果　 (1)FGR组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为(130 5± 2 6 0 ) μg/L、(2 40± 0 42 ) μg/L及(5 5 79± 848) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 6± 1 7) μg/L、(1 5 4± 0 31) μg/L及 (86 9± 183) μg/L。 (2 )巨大儿组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 9 7± 44 6 ) μg/L、(2 43± 0 2 5 ) μg/L及(5 5 6 2± 742 ) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 9 6± 2 3 9) μg/L、(2 19± 0 2 9) μg/L及(16 82± 130 )μg/L。(3)对照组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 7 9± 70 7) μg/L、(2 41± 0 36 )μg/L及 (5 5 86± 6 78) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 8 9     

Ultrasonic prediction of growth discordancy by intertwin difference in abdominal circumference

Intertwin abdominal circumference (AC) and femur length (FL) differences were studied in 24 growth-discordant (greater than or equal to 15% birth weight difference) and in 32-growth concordant twin pairs delivered within 2 weeks of the last ultrasonic examination. Both groups were of similar gestational age but differed significantly in the mean twin birth weight and intertwin AC difference (P = 0.01 and P = 0.00009, respectively). A cutoff value (greater than or equal to 18 mm) for AC difference was found to discriminate significantly (P less than 0.0009) between concordant and discordant pairs with sensitivity, specificity, positive predictive value and negative predictive value of 66.7%, 78%, 69.5% and 75.7%, respectively. These data may suggest that an intertwin difference of 18 mm or more in AC effectively screens for the diagnosis of 15% or more birth weight difference in twin pregnancies.     

Characterization of the growth-discordant twin

A computer-assisted analysis of perinatal variables was undertaken in order to characterize the growth-discordant twin. We studied 124 twin pairs grouped at four degrees of discordancy: over 5, 10, 15, and 20% birth weight difference, using the larger twin as 100%. Twins with birth weight discrepancy below these figures were considered concordant. Highly discordant second twins showed significantly lower birth weight, gestational age, and Apgar scores, and prolonged neonatal hospitalization, as compared with discordant first twins. Complex presentations and a higher cesarean section rate characterize discordant first and concordant twins. It is suggested that a 15% birth weight discordancy be used as the safety limit for birth weight disparity. We also recommend special attention when discordancy seems to increase, especially if the discordant is the second twin.     

Non-invasive method of evaluation of trophoblast invasion of spiral arteries in monochorionic twins with discordant birthweight

To test the hypothesis that variation in birthweight between twin pairs is due to discordant placental development, we determined spiral arterial blood flow by colour pulsed Doppler ultrasound scan. We prospectively studied 24 twin pregnancies in the late second trimester with (n=12) and without (n=12) inter-pair difference in estimated birthweight of > or = 20 per cent. In the discordant growth group, there were seven cases with chronic twin-twin transfusion syndrome (TTTS) and five without. The blood flow in spiral artery of each twin's portion of the placenta was assessed by resistance index (RI) by colour flow pulsed Doppler within a 5 cm radius of cord insertion. In twins with discordant weight, RI was increased in the growth restricted (FGR) twin than the appropriate for gestational age (AGA) co-twin (0.46 +/- 0.02 vs 0.3 +/- 0.01; P< 0.001) and the control group (P< 0.001). However, delta RI was comparable between twins with and without TTTS (0.13 +/- 0.01 vs 0.19 +/- 0.02; P=NS). No such differences were found between concordant twin pairs (0.28 +/- 0.01 vs 0.29 +/- 0.1; P=NS) and AGA twins of the discordant growth group. This study indicates that growth restricted twins have increased resistance to blood flow in the spiral arteries than the AGA co-twins. This observation, therefore, suggests non-physiological remodelling of the maternal spiral arteries in response to migrating trophoblast in placental bed of FGR MC twins.     

Does birth weight discordance in preterm twins affect neonatal outcome?

OBJECTIVE: To compare neonatal morbidity and mortality between hospitalized discordant and concordant preterm twin pairs. STUDY DESIGN: This was a retrospective, hospital-based study of preterm twins, followed in neonatal intensive care unit. Twins were classified as discordant when the difference in birth weight was >15%. Morbidity and mortality rates were compared between discordant and concordant groups. RESULTS: Of 136 preterm twins in the study, 54 were discordant and 82 were concordant. In discordant twins hypoglycemia and cesarean delivery rate was higher than concordant pairs. The mortality rate did not differ between concordant and discordant groups. CONCLUSIONS: Hospitalized preterm discordant twin pairs have an increased risk of hypoglycemia compared to concordants. Discordant growth is not a risk factor for prolonged hospitalization and increased mortality.     

Discordant twins--a prospective study of the diagnostic value of real-time ultrasonography combined with umbilical artery velocimetry

This study was undertaken to evaluate the role of Doppler velocimetry combined with intertwin differences in ultrasonographically derived estimated fetal weight, biparietal diameter, abdominal circumference, and femur length as a comprehensive test for the prediction of discordancy. The following cutoff values were used to indicate abnormal test results: delta biparietal diameter greater than 6 mm, delta abdominal circumference greater than 20 mm, delta femur length greater than 5 mm, delta estimated fetal weight greater than 15%, and delta systolic/diastolic ratio greater than 15%. Discordancy was identified when the birth weight difference exceeded 15%. The study population consisted of 58 consecutively evaluated third-trimester twin gestations. Eighteen sets of twins were discordant. None of these tests was uniformally successful in identifying twin discordancy; in three instances, all test results were normal. The diagnostic accuracy provided by ultrasonography was not significantly different from that provided by Doppler velocimetry. Overall the best predictor appeared to be the presence of either delta systolic/diastolic ratio greater than 15% or delta estimated fetal weights greater than 15%, which correctly identified 14 of the 18 discordant twins and misclassified only five of the 40 concordant pairs. This combination also had the highest positive and negative predictive values (73% and 90%, respectively).     

Sonographic evaluation of growth discordance and chorionicity in twin gestation.

Ninety-four twin gestations had serial ultrasound examinations for evaluation of fetal growth, with special attention to prediction of weight discordance and chorionicity. Fetal weight estimations were made a mean of 3.2 days before birth and then compared to actual birthweights. The average error in intertwin discordance prediction was 1 +/- 9%. In 56 patients ultrasonic detection of membrane thickness was compared with placental pathologic conditions. If a membrane was seen between twins, it was confirmed by placental pathologic study in all cases. No membrane was seen in four twin pairs, but only one of these actually had monochorionic monoamniotic membranes. The three cases with false-positive diagnoses of monoamniotic twin gestation were initially seen late in pregnancy. If clinical decisions in twin gestations are based on ultrasound determination of discordance and chorionicity, the level of accuracy demonstrated by these data must be considered.     

The intrauterine ponderal index in relation to birth weight discordance in twin gestations

Objective: To establish the relationship between the fetal ponderal index and birth weight discordance in twins. Method: The fetal ponderal index (estimated fetal weight ÷ femur length³) was calculated in 86 pairs of twins delivered within 2 weeks of the last sonography and analyzed in relation to birth weight discordance. Results: A weak but significant correlation between fetal ponderal index and birth weight (r = 0.26, P < 0.0007) but no correlation with gestational age (r = 0.035, P = 0.65) were found. Members of concordant pairs (<15% birth weight difference) had a significantly higher fetal ponderal index compared with members of mildly (15–25%) discordant pairs (P < 0.02), but not as compared with members of severely discordant (>25%) pairs. Conclusion: The characteristics of the fetal ponderal index in twins are similar to those in singletons. Fetal size seems to be diminished in severe but not in mild discordants. However, in its present form, the fetal ponderal index is a poor predictor of discordant growth and therefore should be employed cautiously in twin gestations.     

Birth weight in twins: an analysis of discordancy and growth retardation

Sonographic estimation of fetal weight offers the potential of antenatal diagnosis of discordancy and growth retardation in twins. Although standards for intertwin birth weight percent differences in infants over 2500 g are available, similar norms are not available at lower weights. Intertwin birth weight percent differences in live-born twins above 500 g in 500-g increments were analyzed. Intertwin birth weight differences, expressed as a percentage of the weight of the larger twin, were relatively uniform across a wide range of birth weights. Differences above 15% were increasingly more likely to be associated with growth retardation in one of the infants.     

THE AUSTRALIAN & NEW ZEALAND JOURNAL OF OBSTETRICS & GYNAECOLOGY

In order to assess the possible influence of fetal polypeptide hormones on birth size, somatomedin-like receptor activity (SmLRA) (n = 281), prolactin (n = 158), growth hormone (n = 133) and insulin (n = 108) concentrations were measured in the cord blood of 281 singleton infants born after different complications of pregnancy. Infant sex did not significantly affect the concentration of any hormone. SmLRA concentrations appeared to rise from 25 to 38 weeks of gestation, but thereafter fell. Concentrations of prolactin, growth hormone and insulin correlated negatively with gestational age. Insulin emerged as the hormone most clearly related to fetal growth, since concentrations were high (mean +/- SD = 20.6 +/- 11.5 uU/ml) in serum from infants of diabetic mothers (IDM) and other large-for-dates infants (10.1 +/- 4.8 uU/ml), but low (5.3 +/- 0.5 uU/ml) in infants who were small-for-dates (SFD). In contrast, SmLRA concentrations were high in serum from SFD infants (0.63 +/- 0.29 U/ml) and low in IDM (0.43 +/- 0.16 U/ml). Prolactin concentrations were higher in serum from SFD infants (212 +/- 101 ng/ml) and from IDM (237 +/- 182 ng/ml) than from normal infants born at term (139 +/- 68 ng/ml). Administration of intramuscular betamethasone to pregnant women in premature labour resulted in significant elevations in the concentrations of prolactin and insulin in cord blood.     

The effect of birth weight discordance on twin neonatal mortality

OBJECTIVE: To estimate the association between birth weight discordance and neonatal mortality controlling for the effects of fetal growth, and to understand the differences in the incidence of mortality between larger and smaller infants. METHODS: This analysis is based on the National Center for Health Statistics matched multiple birth data set file containing all twin births in the United States from 1995 through 1997. Birth weight discordance was grouped into four levels (15-19%, 20-24%, 25-29%, and 30% or more). Generalized estimating equations were used to obtain adjusted odds ratios and 95% confidence intervals to estimate the mortality risk associated with discordance after adjusting for fetal growth. RESULTS: Mortality was 11 times higher among highly discordant smaller twins (30% or more) compared with nondiscordant smaller twins (43.4 and 3.8 per 1000, respectively). Risk estimates ranged from 1.08 (95% confidence interval 0.85, 1.38) among 15-19% discordant twins to 2.05 (95% confidence interval 1.66, 2.51) among 30% or more discordant twins. Larger twins had similar risk estimates. After accounting for the association between fetal growth and discordance, mortality risk was substantially higher among smaller and larger twins who were highly discordant (30% or more). In addition, there was little difference in the magnitude of risk estimates between highly discordant smaller and larger twins. CONCLUSION: After controlling for fetal growth, smaller and larger twins affected by higher levels of birth weight discordance (25% or more) remain at disproportionate risk for neonatal mortality when compared with other smaller or larger twins. Additionally, smaller twins do not have an elevated risk compared with larger twins after adjusting for their different fetal growth distributions.     

Growth pattern of twins of different chorionicity evaluated by sonographic biometry

OBJECTIVE: To determine differences between growth patterns of monochorionic and dichorionic twins, and of concordant and discordant twins of both chorionicities. METHODS: We studied 70 cases of concordant twins (24 monochorionic, 46 dichorionic) and 45 cases of discordant twins (25 monochorionic, 20 dichorionic). In each case, growth was measured longitudinally by ultrasound biometry and the growth pattern was depicted. RESULTS: There were no differences in incremental growth between concordant monochorionic and dichorionic twins. The growth curve of concordant twins of both chorionicities was almost the same as that of a singleton until 34 weeks' gestation. However, in the discordant twins, the growth of the larger twin matched the growth curve of a singleton or concordant twin, but the growth of the smaller twin gradually decreased to the range of growth restriction. The growth curves for monochorionic discordant twins appeared to be representative of two groups, one of which had onset of discordancy before 24 weeks.CONCLUSION: It is clinically important to determine chorionicity early in twin pregnancies, to calculate the percentage of discordancy between the fetuses, and to examine longitudinal fetal growth curves in each chorionicity.     

脂联素和胰岛素与胎儿生长的关系

目的:探讨脂联素,胰岛素与胎儿生长发育的关系。方法:选取21例分娩生长受限胎儿(FGR组)、21例分娩巨大儿(巨大儿组)及21例分娩正常儿(对照组)的产妇,抽取3组产妇分娩后肘静脉血及其新生儿脐静脉血.分离血清。采用双抗体夹心酶联免疫吸附法和放射免疫法测定3组产妇血清及新生儿脐静脉血清中脂联素和胰岛素的水平。结果:FGR组产妇血清脂联素水平明显低于对照组及巨大儿组(P<0.01);FGR组新生儿脐血清脂联素水平明显低于对照组及巨大儿组(P<0.05);3组产妇血清中脂联素水平均明显低于新生儿脐血清中脂联素水平(P<0.01)。FGR组胎盘重量明显低于对照组及巨大儿组(P<0.01);3组产妇血清及新生儿脐血血清中胰岛素水平差异无显著性(P>0.05)。3组产妇血清脂联素水平与胰岛素水平无相关(P>0.05);3组新生儿脐血清脂联素水平与胰岛素水平呈明显负相关性(P<0.05);3组产妇血清脂联素水平与新生儿脂联素水平无相关(P>0.05);3组产妇血清胰岛素水平和新生儿脐血胰岛素水平无相关性(P>0.05)。3组新生儿脐血清脂联素水平与新生儿出生体重、胎盘重量、新生儿头围、身长、体重/身长比呈明显正相关关系(P<0.05);3组新生儿脐血清胰岛素水平、产妇血清脂联素水平、产妇血清胰岛素水平与新生儿出生体重、胎盘重量、头围、身长、体重/身长比均无相关性。结论:脐血中的脂联素、胰岛素在胎儿宫内生长和发育过程中可能起重要的调节作用,可作为评价胎儿生长发育及体内脂肪储备状态的临床指标之一。胎儿自身分泌的脂联素与胎儿生长关系密切。