Association Between Maternal-Fetal HLA-DR Relationships and Fetal Growth

PROBLEM: To determine whether maternal-fetal human leukocyte antigen (HLA) antigenic relationships are associated with differential fetal growth in weight. METHOD: A cohort of 659 primigravid women were enrolled in this study in the prepartum period and their neonates were subsequently examined. Anthropometric, maternal cigarette smoking behavior, health, pregnancy, and delivery data were collected; serogenetic typing was conducted on maternal and cord bloods to determine maternal and neonatal HLA antigenic phenotypes. Women and their neonates were assigned to one of the four different types of maternal-fetal relationships existing at each of the HLA-A, B, DR, and DQ loci. Birthweights were treated quantitatively and qualitatively (neonates classified as growth-retarded or normal). RESULTS: After controlling for other factors influencing birthweight (e.g., smoking, maternal body size), significantly lower birthweight trends (P < .01) were found when neonates expressed a single HLA-DR antigen and their mothers expressed a second HLA-DR antigen that was foreign (allogeneic) to their neonate. CONCLUSION: Our finding supports the hypothesis that lack of maternal immune exposure to fetal HLA antigens is associated with a slowing of fetal growth. However, in this situation slowed fetal growth is most likely to occur when the fetus is potentially exposed to maternal HLA-DR alloantigens. We believe this sheds new light on immunologic events at the maternal-fetal interface influencing fetal growth. We present one possible explanation to account for this finding.     

IGF-I与宫内发育迟缓及其结合蛋白的关系

目的：检测宫内发育迟缓（IUGR）儿脐血胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子结合蛋白-3（IGFBP-3）水平,分析这些指标的变化程度与胎儿期生长的关系。方法：将86例脐血标本分为IUGR（即小于胎龄儿）组和适于胎龄儿（AGA）组。采用放射免疫分析（RIA）测定IGF-I水平,免疫放射分析（IR-MA）测定IGFBP-3水平。两组间比较用t检验,两变量之间的关系采用相关回归分析。结果：与AGA组相比,IUGR组脐血IGF-I和IGFBP-3水平显著降低（P均〈0.01）;IGF-I、IGFBP-3均随胎龄及出生体重增加而增加（P均〈0.01）;IGFBP-3与IGF-I呈正相关（P〈0.01）。结论：脐血IGF-I和IGFBP-3的含量可作为判断新生儿生长发育程度的一项客观指标。     

Immunohistochemical Findings in Acute Atherosis Associated With Intrauterine Growth Retardation

ABSTRACT: Lesions of acute atherosis in 23 placentas from pregnancies complicated by fetal growth retardation (less than tenth percentile) were studied by an immunoperoxidase staining. Twelve of them were from normotensive pregnancies, ten complicated by pregnancy induced hypertension, and the remaining associated with systemic lupus erythematosus. Twentythree placentas with physiological changes of the spiral arteries corresponding to normal pregnancies served as controls. Six of the cases complicated by fetal growth retardation showed absence of physiological changes in basal decidua. Massive intramural granular deposits of IgM, a smaller amount of C3 and C1q, and slight deposits of IgA and IgG were found in vessels with acute atherosis. No intramural deposition of immunoglobulins or complement was observed in vessels with or without physiological changes. The presence of granular deposits of immunoglobulins and complement within the vessel walls with acute atherosis may be related to an immunological disorder, probably mediated by immune complexes.     

宫内生长迟缓胎儿脐血IGF-Ⅰ及IGFBP-3水平观察

目的：探讨新生儿脐血中胰岛素样生长因子-I（IGF-I）和胰岛素样生长因子结合蛋白-3（IGFBP-3）水平与胎儿宫内生长发育的关系。方法：采用放射免疫分析,分别对出生时体重正常新生儿与宫内生长迟缓的低体重新生儿脐血的IGF-I及IGFBP-3水平进行检测。结果：宫内发育迟缓组新生儿脐血的IGF-I及IGFBP-3的含量明显低于正常对照组（P〈0.01）,有显著差异性。结论：：IGF-I和IGFBP-3与胎儿宫内生长发育密切相关,对胎儿的宫内生长发育起着重要的调节作用。     

L-精氨酸治疗对胎儿宫内发育迟缓孕妇血液流变性的影响

目的 :探讨L 精氨酸 (L Arg)治疗对胎儿宫内发育迟缓 (IUGR)孕妇血液流变性的影响。方法 :选择符合入选条件的IUGR患者 6 6例 ,其中常规治疗组 35例 ,予以常规治疗 ;L Arg组 30例 ,在常规治疗的基础上加用L Arg治疗。另外 ,选择正常初产妇 31例为正常对照组。监测治疗前后孕妇血液流变学参数变化。结果 :治疗后 ,L Arg组全血低切粘度 (LBV)值较常规治疗组显著降低(P <0 .0 5)。结论 :L Arg能改善IUGR孕妇的血液流变学部分指标。     

Primary Chronic Abortion,Preeclampsia, Idiopathic Intrauterine Growth Retardation,Hydatidiform Mole,and Choriocarcinoma: A Unifying Concept

ABSTRACT: Different degrees of maternal hyporesponse, as far as blocking activity is concerned, are proposed for primary chronic abortion, preeclampsia, and idiopathic intrauterine growth retardation. On the other hand, a maternal hyperresponse to fetal antigens with a higher production of blocking antibodies may be related to an unusual proliferation of the trophoblast in cases of hydatidiform mole and choriocarcinoma.     

Histocompatibility antigens in progressive systemic sclerosis (PSS; scleroderma)

Patients with progressive systemic sclerosis (PSS; scleroderma) were typed for the HLA-A, -B, and -DR antigens. No significant differences in the frequencies of any HLA-A or -B antigen were found. In the subgroup of patients with PSS and diffuse scleroderma (PSS-DS), the frequency of Bw35 was increased (0.30 vs 0.17 in controls;P<0.005, correctedP>0.2). Although patients with PSS-DS also had an increased frequency of DR1 antigen (0.27 vs 0.12 in local controls;P<0.005, correctedP<0.05), no association between Bw35 and DR1 antigens could be detected. We found no increase in the frequencies of the DR3 or DR5 antigens in patients with PSS. However, in a subset of PSS patients with pulmonary fibrosis, an increase in DR3 and a decrease in DR4 antigens (P<0.005) were observed. Serum antibodies to centromere occurred more frequently in DR1-positive than DR1-negative patients (0.46 vs 0.18;P<0.005). This study of a large number of patients with PSS failed to confirm previously reported associations of PSS with the HLA-B8/DR3 haplotype or HLA-DR5 antigen.     

Cerebral Utilization of Glucose,Ketone Bodies and Oxygen in Starving Infant Rats and the Effect of Intrauterine Growth Retardation

Cerebral arteriovenous differences of acetoacetate, D-β-hydroxybutyrate, glucose, lactate and oxygen and brain DNA content was measured at 20 days of age in intrauterine growth retarded (IUGR) rats and normal littermates after 48 and 72 h of starvation. Cerebral blood flow (CBF) was measured with labeled micro-spheres in other comparable groups of IUGR and control rats. CBF was similar in IUGR and normal littermates (0.57±0.09 and 0.58±0.10 ml/min respectively). After 48 h of starvation, arterial glucose was significantly lower in IUGR than control animals but the arterial concentrations of ketone bodies were similar. After 48 h of starvation, cerebral arteriovenous difference of β-hydroxybutyrate was significantly higher in control than IUGR rats also when expressed per mg brain DNA as was the fractional uptake of D-p-hydroxybutyrate. After 72 h of starvation, arterial concentrations of ketone bodies were significantly lower in IUGR rats than controls but the fractional uptake of D-β-hydroxybutyrate was increased compared to IUGR rats starved for 48 h. The average percentage of calculated total substrate uptake (μmol/min) accounted for by ketone bodies increased in control animals from 31.1 % after 48 h of starvation to 41.0% after 72 h of starvation. In IUGR rats these percentage values were 26.5 and 25.7 respectively. After 72 h of starvation the fraction of total cerebral uptake of substrates accounted for by ketone bodies was significantly higher in control than IUGR rats. As total cerebral uptake of substrates was similar between IUGR and control animals it is concluded that IUGR rats are more dependent on glucose as a substrate for the brain during starvation.     

健胎液对胎儿宫内发育迟缓孕鼠血浆、胎盘NO含量的影响

为从孕鼠血浆和胎盘一氧化氮（ＮＯ）水平探讨中药“健胎液”治疗胎儿宫内发育迟缓（ＩＵＧＲ）的机理，采用被动吸烟法建立ＩＵＧＲ动物模型，应用镀铜镉还原和内标比色法（Ｇｒｅｉｓ法），测定ＩＵＧＲ组、ＩＵＧＲ加健胎液组（用药组）孕鼠血浆及胎盘组织中ＮＯ的稳定代射终产物亚硝酸基／硝酸基（ＮＯ－２／ＮＯ－３）含量，并以正常孕鼠作对照。结果：与正常对照组和用药组相比，ＩＵＧＲ组胎鼠平均出生体重显著降低（Ｐ＜００１），ＩＵＧＲ组血浆及胎盘组织中ＮＯ－２／ＮＯ－３含量均显著降低（Ｐ＜００５～００１），而用药组和正常组相比，胎鼠平均出生体重、血浆及胎盘组织中ＮＯ－２／ＮＯ－３含量均无显著性差异（Ｐ＞００５）。结论：胎儿宫内发育迟缓的发生与ＮＯ的合成和释放显著降低，因而影响胎盘微循环，限制了母儿宫内发育迟缓。     

Expression of insulin-like growth factor in the placenta of intrauterine growth-retarded human fetuses

Many cases of intrauterine growth retardation (IUGR) are the result of placental and fetal tissue insufficiency. Insulin-like growth factor-I (IGF-I) is known to play a role in placental and fetal growth. An immunocytochemical study was performed to localize IGF-I peptides in human placenta and umbilical cords of normal (n = 3) and IUGR (n = 3) fetuses. The peripartum fetal conditions were evaluated as well. Immunoreactive IGF-I was detected in the cytotrophoblast, syncytiotrophoblast, amnion, endothelial cells of fetal capillaries and in the decidua in both normal and IUGR placental tissue. A more robust immunostaining and increased numbers of positively stained cells were found in the decidua of IUGR placenta (p < 0.001). Intense immunostaining was also found in endothelial cells, smooth muscle cells and fibroblasts of the umbilical vein. IGF-I immunoreactivity was also present in stroma (Hofbauer cells and/or fibroblasts) of IUGR villi. Our results indicate that expression of IGF-I is high in specific sites in placenta and umbilical cords, which indicates a paracrine and/or endocrine function. The increased expression of IGF-I in placenta of IUGR fetuses indicates its involvement in restoring normal growth by means of a positive feed-back mechanism.     

胎儿宫内发育迟缓孕妇经高压氧治疗出生后新生儿1年随访结果分析

目的 探讨高压氧治疗胎儿宫内发育迟缓(IUGR)胎儿的远期疗效。方法 经高压氧治疗和正常出生的新生儿48例分二组分别在出生后3个月、6个月、9个月、12个月为期一年的随访，对照新生儿的身长、体重、智能发育情况。结果 经高压氧治疗后的新生儿发育正常，各观察指标与正常出生的新生儿比较无明显差异。结论 高压乳治疗IUGR孕妇不但宫内治疗疗效可靠，且远期效果好，值得推广使用。     

Heart Rate Changes During a Fixed Reaction Time Task in Normal and Retarded Adult Males

The relationship between heart rate (HR) changes and fixed reaction time (RT) performance was studied in groups of normal and mentally retarded male Ss. Each 5 received blocks of 15 RT trials during 4-, 7-, and 13-sec preparatory intervals. Heart rate was continuously monitored. The results revealed that retarded Ss had significantly slower RT scores, significantly lower basal HR, and lower magnitude HR decelerations prior to reaction signal onset when compared to normal Ss. These group differences were apparent in all three preparatory interval conditions and were interpreted to indicate less accurate covert timing of PI length in retarded 5s. Correlations between HR deceleration (measured during the sec in which the reaction signal occurred) and RI scores lent support to the notion that significant HR deceleration accompanies fast RT responding in all but the 13-sec PI condition for retarded Ss. In this condition, HR acceleration was related to fast RT performance in retarded Ss. It was suggested that in the 13-sec PI, retarded Ss exhibited a dissociation between somatic and autonomic response systems which might he related to an information processing deficit in tasks of extended duration.     

妊娠中、晚期300例胎儿脐血染色体核型分析

目的 分析妊娠中、晚期胎儿脐血染色体核型,了解该时期异常核型出现的频率、类型及与各种产前诊断指征的关系。方法 ３００例有产前诊断指征的孕妇,在妊娠１８～３８孕周时穿刺胎儿脐带血管,帛脐箅查染色体核型。结果 发现异常核型２３例（７．７％）,其中２１三体占３９．１％（８／１２６）,Ｐ＝０．７７。三体为主要的染色体异常,占异常核型的６０．９％（１４／２３）。其中２１三体占３９．１％（９／２３）,平衡易位     

Immunohistochemical analysis of neural cell adhesion molecule (N-CAM) and pan-cadherin in the small intestine of intrauterine growth-retarded newborn rats caused by maternal protein malnutrition

Cell-cell and cell-matrix adhesion molecules play an important role in morphogenesis, cell signaling and are involved in cell proliferation, cell death, cell polarization and differentiation. In the present study, we investigated N-CAM and pan-cadherin expression in small intestine of intrauterine growth-retarded (IUGR) newborn rats after maternal protein malnutrition during pregnancy. N-CAM and pan-cadherin immunostaining was increased in small intestine of IUGR newborn rats. This increase was evident in epithelial cells on villi, lamina propria, submucosa, muscularis mucosa and muscularis externa. The increase in numbers of villous N-CAM-positive and pan-cadherin-positive epithelial cells was statistically significant (p < 0.001). In most areas, crypts did not show any immunopositive epithelial cells or showed decreased expression of the adhesion molecules. Although the villous height was decreased in IUGR rats, the decrease was statistically not significant. Expression and recruitment of N-CAM and pan-cadherin in small intestine of newborn IUGR rats may indicate a direct or indirect involvement of adhesion mechanisms or signaling in the growth retardation process.     

Bilateral branchial cleft sinuses associated with intrauterine and postnatal growth retardation,premature aging,and unusual facial appearance: A new syndrome with dominant transmission

A mother and son with bilateral branchial sinuses, intrauterine and postnatal growth retardation, unusual facial appearance, and premature aging in the mother are reported. No other members of the family are similarly affected. No hormonal or systemic cause of growth retardation was identified. Chromosomal studies with G-banding were normal. It is suggested that this syndrome is a dominant trait, the mother being the initial mutant.     

Intrauterine Growth Retardation of Unknown Etiology. I. Serum Complement and Circulating Immune Complexes in Mothers and Infants

ABSTRACT: Complement (C) and circulating immune complexes (CIC) levels were measured in 22 full-term pregnant women and 15 of their small-for-gestational-age (SGA) offspring in order to seek evidence supporting an immunological etiology for placental lesions related to idiopathic intrauterine growth retardation. We used 19 normal full-term pregnant women and 18 of their infants with birthweight above the 25th centile of the ponderal curve as a control population for this study. C levels were significantly lower in mothers of SGA infants than in controls (146.6 ± 46.6 and 183.6 ± 36.6 respectively, p < 0.01). CIC were present in the sera of 5 out of 22 mothers of the SGA group and in 3 out of the 15 infants sera. No CIC were found in the sera of mothers or infants from the control group. Placental lesions were observed in 14 out of the 22 (64%) cases studied in the SGA group and in 1 of 11 (9%) of the controls. Two placentas from SGA infants showed acute atherosis, and deposits of IgM and C₃ were found in their vessel walls. These data are in favor of an immunological mechanism for intrauterine growth retardation of unknown etiology.     

Trisomy 9 confined to the placenta: Prenatal diagnosis and neonatal follow-up

Chorionic villus sampling (CVS), performed on a woman in the 23rd menstrual week because of bilateral fetal hydronephrosis and suspected intrauterine growth retardation (IUGR), documented trisomy 9 in all cells examined. Chromosomes of amniocytes and fetal blood lymphocytes were normal. The ongoing pregnancy was monitored closely, and at 37 weeks, a phenotypic normal male infant was delivered. Multiple placental biopsies showed 47,XY,+9, while a repeat chromosome analysis of the infant and biopsies from the amniotic membrane were normal (46,XY). This case further emphasizes the association between placental aneuploidy and IUGR. To our knowledge, nonmosaic trisomy 9 in CVS confined to the chorionic villi and later confirmed in the placenta has not been reported previously.     

Guadalajara camptodactyly syndrome type II

Two sisters and an unrelated girl presented a distinct intrauterine growth retardation-malformation syndrome with short stature, microcephaly, pectus excavatum, hip dislocation, hypoplastic pubic region and genitalia, camptodactyly, talipes, shortened 2nd toes, hypoplastic patella and skeletal dysplasia probably due to homozygosity from an autosomal recessive gene.