Congenital malformations in the newborn--a prospective study

In a prospective study of 4098 births the incidence of congenital malformations was 1.464 per 100 births. Major malformations were seen in 1.1% births and minor malformations in 0.4% births. Patterns of congenital anomalies included multiple anomalies (37.68%), CNS malformations (13.33%), alimentary tract anomalies (6.66%), cardiovascular malformations (8.99%), genitourinary malformation (6.66%), limb anomalies (13.33%), and anomalies of skin and appendages (13.33%). Factors like maternal age, hormone testing and drug ingestion during pregnancy, radiation exposure and maternal infections were identified as possible risk factors for congenital malformations in the newborn.     

Thiamin status of the offspring of diabetic rats

Erythrocyte transketolase activity and thiamin pyrophosphate effect were examined in the offspring of streptozotocin-diabetic rats. Thiamin reserve was found to be significantly reduced in litters of untreated diabetic rats as compared to control and to insulin-treated diabetic rats. Supplementation of the untreated diabetic dams throughout pregnancy with oral thiamin was associated with a significantly improved thiamin status of the litters. We conclude that, due to enhanced fetal glucose turnover during diabetic gestation, a fetal thiamin deficiency state may evolve; this condition can be remedied with maternal thiamin supplementation.     

Congenital malformations in the southeast of Sweden--a registry study with validation

A study was made of the occurrence of congenital malformations in the southeast region of Sweden, utilizing all available relevant health registries. Östergötland county had been pinpointed in a routine surveillance as having an increased malformation risk. Various validations of the register data were undertaken and different types of errors were detected. An increased risk was seen, in Östergötland county compared to the reference counties, for specific types of malformations: preauricular appendices, pylorostenosis, uterine/vaginal malformations, foot deformities, limb reduction defects and cardiovascular malformations. Variable classification or registration artefacts explained the excess among the first four conditions. Limb reduction defects were also mis‐coded, but the increased risk in Östergötland county may persist. Conclusion: There is an increased risk of major cardiovascular malformations in Östergötland county compared to the reference counties that also shows an uneven distribution within the county.     

Increased renal tubular reabsorption of calcium and magnesium by the offspring of diabetic rat pregnancy

Diabetic pregnancy has a marked influence on offspring calcium and magnesium homeostasis. Urinary excretion of calcium and magnesium is reduced, yet offspring of diabetic pregnancy exhibit hypomagnesemia and hypocalcemia. The aim of this study was to measure renal hemodynamic and tubular function in the offspring of diabetic (OD) and control, nondiabetic (OC) rats at 4 and 8 wk of age to determine the glomerular and tubular mechanisms through which renal calcium and magnesium handling are programmed in utero. The fraction of filtered calcium that was excreted was significantly lower in OD at both 4 and 8 wk of age [8 wk: OC (n = 6), 11.8 +/- 2.9 versus OD (n = 5), 4.3 +/- 0.6%; p < 0.05] and that of magnesium was lower at 8 wk of age [OC (n = 6), 42.4 +/- 7.5 versus OD (n = 5), 13.0 +/- 1.7%; p < 0.01]. This increased reabsorption occurred despite an elevated GFR in OD. These findings clearly indicate that tubular reabsorptive mechanisms for calcium and magnesium are increased markedly in OD. Serum PTH concentration was reduced in 8-wk-old OD [OC (n = 7), 539.4 +/- 142.1 versus OD (n = 9), 174.3 +/- 69.4 pg/ml; p < 0.05], consistent with previous reports in human infants. Taken together, these observations suggest that the basis for the altered renal magnesium and calcium handling in OD involves increased tubular transport activity and possibly increased sensitivity of these mechanisms to PTH.     

Congenital cardiovascular malformations in twins and triplets from a population-based study

Data from the Baltimore-Washington Infant Study of congenital cardiovascular malformations permitted detailed analysis of congenital cardiovascular malformations in 62 twins and 3 triplets and 2303 singleton cases. A probability sample of controls (n = 2793) included 43 twins. The case prevalence of multiple births was 28 of 1000, compared with a 15 of 1000 prevalence among controls (chi 2 = 5.7). There were more girls among case twins than among case singletons and controls (chi 2 = 9.0). Monozygosity was no more frequent in case twins than in controls. Looping defects occurred in 4 monozygotic twin pairs compared with only 1 dizygotic twin pair. The twinning process itself may be implicated in the development of congenital cardiovascular malformations in some of these infants, especially those with looping defects, but concordance of types of defects in 4 of 65 pairs implicates genetic factors in the determination of some forms of congenital cardiovascular malformations.     

肋-软骨连结损伤对胸廓发育影响的实验研究

目的探讨多根肋-软骨连结（CCJ）损伤对胸廓发育的影响。方法取20只4周龄SD大鼠随机分成二组，每组10只，分别行左侧第5～7肋CCJ分离或切除。术前、术毕及术后定期测量胸围并作前后自身对照和组间比较；术后12周处死动物取胸廓标本，测量受术肋骨及肋软骨长度进行两侧自身对照。结果两组的胸廓外观均未见明显畸形。术毕CCJ切除组胸围较术前缩小（P〈0．05），术毕和术后1周CCJ切除组胸围较分离组小（P〈0．05），但2周后组间差异无统计学意义（P〉0．05）。CCJ切除组第6、7肋骨及第5～7肋软骨长度两侧比较差异有显著性意义（P〈0．05），但在CCJ分离组仅受术侧第6肋较对侧短（P〈0、05）。结论多根肋骨CCJ切除或分离对术后胸廓的发育均有影响，其中CCJ切除对胸廓的继续发育影响较大。     

Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats

Maternal diabetes causes a range of complications in offspring, including reduced skeletal ossification. This study examined whether feeding gamma-linoleic acid (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves skeletal development in their offspring. In addition, Ca(2+) concentration was monitored in maternal plasma and fetal tissue, as well as placental mRNA expression of calbindin-D(9k). Female rats rendered diabetic with streptozotocin were fed GLA (500 mg/kg/d), ascorbate (290 mg/kg/d), ascorbyl-GLA (790 mg/kg/d), or GLA and ascorbate (500 and 290 mg/kg/d, respectively) throughout pregnancy. Fetal skeletons were studied after alizarin red staining. Fewer ossification centers were observed in offspring of diabetic rats compared with offspring of control rats (68 +/- 4% of control, p = 0.01). An almost complete restoration of ossification occurred with all the treatments (92-95 +/- 3% of control). The effects of treatment on fetal ossification could not be explained by altered maternal plasma Ca(2+) concentrations or by mRNA expression of the placental Ca(2+)-transporting protein calbindin-D(9K). We conclude that GLA and/or ascorbate treatment was effective against diabetes-induced fetal ossification defects by a mechanism not related to placental Ca(2+) supply.     

胚胎期铅暴露对子代大鼠摄食和排便行为的影响及可能机制

目的探讨胚胎期铅暴露对子代大鼠摄食、排便行为的影响及可能机制。方法采用SpragueDawley大鼠孕期自由饮用0.1%(低剂量铅暴露组)和0.2%醋酸铅(高剂量铅暴露组)溶液的方法建立胚胎期铅暴露模型,并设空白对照组。将各组母鼠娩出的雄性仔鼠纳入研究,各组分别取10只仔鼠观察其在摄食、排便、胃排空、小肠推进及胃黏膜病理性炎性反应等方面的变化特点;各组分别取8只仔鼠,应用电镜技术、免疫组化等方法从空肠微绒毛及细胞连接超微结构变化,以及摄食中枢胆囊收缩素-8(CCK-8)、胃动素(MTL)的表达等方面揭示胚胎期铅暴露仔鼠胃肠动力异常的可能机制。结果与对照组比较,高、低剂量铅暴露组仔鼠每日摄食量下降,粪便含水量增加,粪粒质量减少,小肠推进速度增加(P0.05);高剂量铅暴露组仔鼠胃排空能力较对照组下降(P0.05)。与对照组比较,胚胎期铅暴露仔鼠胃黏膜出现明显的病理炎性改变(P0.05);空肠微绒毛减少、长度短缩及上皮间桥粒数目减少、致密斑间隙扩大(P0.05);摄食中枢MTL、CCK-8表达增加(P0.05);上述改变的程度与铅暴露剂量间有剂量-效应关系。结论胃肠结构损害程度,以及CCK和MTL在中枢的表达水平具有铅剂量依赖性,这可能是胚胎期铅暴露仔鼠出现异常的摄食、排便及消化功能改变的重要机制。     

母孕前和孕期高脂饮食对新生仔鼠骨骼生长的影响及机制探讨

目的 观察母鼠孕前和孕期高脂饮食对新生仔鼠骨骼生长的影响,并探讨影响骨骼生长的机制.方法 40 只雌性Sprague-Dawley 大鼠随机分为高脂组和对照组(n=20),分别喂养35% 高脂饲料和普通饲料.喂养8 周后,高脂组和对照组各取8 只雌鼠观察其肝脏组织病理;其余与普通饲料喂养的雄性大鼠交配,孕期分别继续给予高脂饲料或普通饲料喂养.待娩出新生仔鼠后24 h 内,测量两组仔鼠体长(鼻尾长度);酶联免疫吸附试验测定血清胰岛素样生长因子-I(IGF-I)水平;光镜下观察肝脏组织病理;免疫组织化学法检测长骨(胫骨、股骨)中胰岛素受体底物1(IRS-1)和磷酸化IRS-1(Phospho-IRS-1)的表达;蛋白质印迹技术检测长骨软骨细胞中促分裂原活化蛋白激酶(MAPK)和磷酸化MAPK(Phospho-MAPK)、磷酯酰肌醇3-激酶(PI3K)和磷酸化PI3K(Phospho-PI3K)、蛋白激酶B(AKT1)和磷酸化AKT1(Phospho-AKT1)的蛋白表达.结果 高脂组仔鼠的出生体长较对照组显著降低(P<0.05).高脂组仔鼠血清IGF-I 水平较对照组下降,但差异无统计学意义(P>0.05).高脂组母鼠及仔鼠肝组织可见脂肪样变,而对照组肝脏病理形态正常.两组仔鼠长骨软骨细胞中IRS-1 的表达差异无统计学意义(P>0.05).高脂组仔鼠长骨软骨细胞中MAPK 的表达水平高于对照组(P<0.05),而PI3K 及AKT1/Phospho-AKT1 的表达水平在两组间差异无统计学意义(P>0.05).结论 母鼠孕前和孕期高脂饮食会影响胎鼠在宫内的骨骼发育,可能与IGF-I 的下降有关,但未发现IGF-I 对骨骼影响的确切发病机制.     

Plasma amino acids in diabetic pregnant rats and in their fetal and adult offspring

Amino acid profiles and total amino-acid concentrations are established in nonfasting plasma of pregnant control, mildly diabetic and severely diabetic rats, and of their fetal and adult offspring. In pregnant rats at day 20 of gestation plasma amino acids can be regarded as normal in mildly diabetic mothers, but are significantly decreased in severely diabetic mothers. In fetuses of control rats, amino acid levels are twice as high as in the mother (fetomaternal ratio 2.0); in the fetuses of mildly diabetic mothers they are significantly lower than normal (fetomaternal ratio 1.3); in the fetuses of severely diabetic mothers they are also significantly lower than normal but with a normal fetomaternal ratio (fetomaternal ratio 2.0). In adult offspring of mildly diabetic mothers the concentration of almost all amino acids as well as that of total amino acid pool is significantly lower than in the controls; in the offspring of severely diabetic mothers they can be regarded as normal. No specific amino acid or group of amino acids can be held responsible for any of these changes, since all differences with control values display an overall effect, involving all or almost all amino acids.     

Congenital cytomegalovirus infection: the impact of cerebral cortical malformations

Aim: Cytomegalovirus has been suggested to have a teratogenous influence during the migration of neural cells from the ventricular zones to the cortex during the gestational period. The aim of this study was to investigate the prevalence of congenital cytomegalovirus infections in a cohort of children with neurological disability and cerebral cortical malformations recognized by neuroimaging. Methods: Twenty‐six children with neurological disability and cerebral cortical malformations were investigated retrospectively for congenital cytomegalovirus infection by analysing the dried blood spot samples for cytomegalovirus deoxynucleic acid using qualitative polymerase chain reaction. Results: CMV DNA in the dried blood spot samples was found in four out of 26 children. Two of these four had severe disabilities with mental retardation, autism, spastic cerebral palsy, epilepsy and deafness. A third child had epilepsy and unilateral cerebral palsy, while the fourth had a mild motor coordination dysfunction and hearing deficit. Conclusion: In our study, the number of congenital cytomegalovirus infections in children with cerebral cortical malformations was higher (4/26) than expected with reference to the birth prevalence (0.2–0.5%) of congenital cytomegalovirus infection in Sweden. We thus conclude that congenital cytomegalovirus infection should be considered in children with cortical malformations of unknown origin.     

100例先天畸形患儿细胞遗传学分析

染色体病是由于染色体数目或结构异常而引起的一类遗传性疾病,染色体畸变可导致患儿智力低下、发育迟缓及先天畸形等一系列临床症状.先天畸形涉及诸多因素,但遗传因素不容忽视.