Utility of finger maze test for learning and memory abilities in infants of cynomolgus monkeys exposed to thiamazole

A new type of learning and memory test using a finger maze was conducted in infant cynomolgus monkeys that were exposed to thiamazole (2 and 3.5 mg/kg per day to pregnant animals orally) during the fetal period (gestational days 120 to 150). We modified Tsuchida's original finger maze test method by reducing the number of trials per day and simplifying the criteria for achievement of training, and we added a long‐term memory test. In the memory test, thiamazole‐exposed infants required greater time to complete the finger maze test than the control infants although no effect was noted in the training or learning test. The results suggest that an impaired long‐term memory could be detected by our modified finger maze test.     

Different outcomes of neonatal thyroid function after Graves' disease in pregnancy: patient reports and literature review

Graves' disease in pregnancy is a rare condition that directly affects neonatal thyroid function. We describe three newborns born to mothers with Graves' disease and discuss differences in outcomes and management. The first infant presented with a goiter at birth but was euthyroid and did not require therapy. The second infant presented with thyroid storm and the third infant present with neonatal hyperthyroidism, and both required treatment with antithyroid drugs. There was documented elevation of maternal and infant thyroid stimulating hormone immunoglobulin (TSI) levels in all three infants. Management of an infant born to a mother with Graves' disease should include monitoring of both maternal and neonatal thyroid function, and maternal TSI levels during pregnancy. Treatment may be needed if the newborn is symptomatic. With clearance of maternal antibodies and antithyroid drugs, manifestations of abnormal thyroid function in the neonate gradually regress, including eventual resolution of a goiter, if initially present.     

Thyroid function in term newborn infants with congenital goiter.

Eighty-four term newborn infants without goiter and 45 newborn infants with congenital goiter were studied with regard to thyroid function. The radiologic development of the femoral and tibial epiphyses was evaluated in those with goiter. Fifty-eight percent of the patients had retarded bone age, markedly elevated TSH levels, elevated TBI, decreased total T4I, and decreased PBI values. Forty-two percent of newborn infants with congenital goiter had a normal bone age, normal values for TSH, PBI, and total T4I, and elevated values for TBI. It is concluded that the 58% of the newborn infants with congenital goiter had subtle hypothyroidism. They require substitution therapy with thyroid hormones in order to avoid possible retardation of normal brain development. Patients with congenital goiter who have no biochemical evidence of hypothyroidism should also be treated with thyroid hormones to achieve rapid regression of goiter.     

早产儿暂时性甲状腺功能低下替代治疗临床研究进展

早产儿暂时性甲状腺功能低下(THOP)发生率高,是否给予甲状腺素替代治疗存在分歧.有关THOP的临床研究提示,THOP甲状腺素替代治疗不能降低病死率、呼吸疾病发生率,可降低动脉导管未闭的发生率.胎龄小于28周THOP早产儿给予甲状腺素替代治疗可能改善神经发育预后,胎龄大于28周不能改善神经发育.未来研究应按胎龄确定早产儿甲状腺素正常值;设计良好的根据胎龄分层的临床随机研究,以明确甲状腺素替代治疗对远期神经发育的影响.     

早产儿暂时性甲状腺功能低下替代治疗临床研究进展

早产儿暂时性甲状腺功能低下(THOP)发生率高,是否给予甲状腺素替代治疗存在分歧.有关THOP的临床研究提示,THOP甲状腺素替代治疗不能降低病死率、呼吸疾病发生率,可降低动脉导管未闭的发生率.胎龄小于28周THOP早产儿给予甲状腺素替代治疗可能改善神经发育预后,胎龄大于28周不能改善神经发育.未来研究应按胎龄确定早产儿甲状腺素正常值;设计良好的根据胎龄分层的临床随机研究,以明确甲状腺素替代治疗对远期神经发育的影响.     

LONG-TERM FOLLOW-UP OF PREVIOUSLY SEPARATED PIGTAIL MACAQUES: GROUP AND INDIVIDUAL DIFFERENCES IN RESPONSE TO NOVEL SITUATIONS

A follow-up study of monkeys who experienced maternal separations as infants 2.5-4.9 years earlier was performed. Matched pairs of previously separated and nonseparated control monkeys were observed individually in four unfamiliar situations, and their behavioral responses and plasma cortisol levels were measured. Results indicated that previously separated animals displayed more disturbance than did their matched controls, and levels of disturbance were significantly correlated with the degree of behavioral and physiological disturbance displayed during the original maternal separations. The results support the idea that the perception of the maternal separation may be a significant factor in whether long-term behavioral deficits exist in social and emotional functioning.     

Perinatal cocaine and methamphetamine exposure: maternal and neonatal correlates

Maternal and neonatal growth, behavior, and physiologic organization were evaluated in 104 mother-infant pairs with positive results of urine toxicology screens. ANOVA comparison of cocaine, methamphetamine, and cocaine plus methamphetamine groups revealed no significant differences in perinatal variables. The Finnegan withdrawal scoring scheme demonstrated that all three groups of infants had altered neonatal behavioral patterns, characterized by abnormal sleep patterns, poor feeding, tremors, and hypertonia. Infants exposed to cocaine or methamphetamine or both were combined and compared with both narcotic-exposed and drug-free mother-infant pairs matched for known maternal risk factors. All drug-exposed groups had significantly higher rates of prematurity and intrauterine growth retardation and smaller head circumferences than did the drug-free comparison group. A significantly higher rate of placental hemorrhage occurred in the cocaine plus methamphetamine group. Stepwise multiple regression analysis assessed the independent contribution of maternal factors; cocaine or methamphetamine was adversely, negatively associated with gestational age, birth weight, length, and occipitofrontal circumference. The increased rate of prematurity, intrauterine growth retardation, and perinatal complications associated with perinatal exposure to cocaine or methamphetamine was greater than that predicted by coexisting risk factors and was consistent with the pharmacologic properties of these drugs.     

Thyroid function tests in preterm infants born to preeclamptic mothers with placental insufficiency

OBJECTIVE: Since preeclampsia causes placental insufficiency, it can be hypothesized that it decreases placental passage of thyroxine (T4) from mother to infant and thus may deepen the transient hypothyroxinemia seen in preterm infants after birth. The aim of this study was to compare thyroid function tests of preterm infants born to preeclamptic mothers with placental insufficiency with preterm infants born to mothers without placental insufficiency. METHODS: Thirty-one preterm infants born to preeclamptic mothers with placental insufficiency were included in the study (group I) and 31 preterm infants born to mothers without placental insufficiency were included as the control group (group II). Thyroid hormone levels were assayed from blood samples obtained from the women before birth and thereafter from the infants at delivery (cord) and on the 1st, 3rd, 7th, and 21st days of life. RESULTS: Cord blood triiodothyronine (T3), free T3 (FT3) and free thyroxine (FT4) levels in group I were lower than in group II, whereas thyrotropin (TSH) and thyroxine binding globulin (TBG) levels were higher. No statistical difference in hormone levels studied at postnatal 1st, 3rd, 7th, and 21st day was found between the two groups. CONCLUSION: Low levels of thyroid hormones and high level of TSH in cord blood in premature infants born to preeclamptic mothers with placental insufficiency suggest intrauterine hypothyroidism. Increase in TSH and thyroid hormone concentrations after birth reveal that the hypothalamic-pituitary-thyroid axis is intact.     

Determinants of fetal growth and body proportionality

Previous studies of fetal growth and body proportionality have been based on error-prone gestational age estimates and on inappropriate comparisons of infants with dissimilar birth weights. Based on a cohort of 8719 infants with validated (by early ultrasonography) gestational ages and indexes of body proportionality standardized for birth weight, potential maternal and fetal determinants of fetal growth and proportionality were assessed. Maternal history of previous low birth weight infants, pregnancy-related hypertension (particularly if severe), diabetes, prepregnancy weight, net gestational weight gain, cigarette smoking, height, parity, and fetal sex were all significantly associated with fetal growth in the expected directions. Consistent with previous reports, maternal age, marital status, and onset or total amount of prenatal care had no significant independent effects. Fetal growth ratio (relative weight for gestational age), pregnancy-related hypertension, fetal sex, and maternal height were the only significant determinants of proportionality. Infants who were growth-retarded, those with taller mothers, those whose mothers had severe pregnancy-related hypertension, and males tended to be longer and thinner and had larger heads for their weight, although these variables explained only a small fraction of the variance in the proportionality measures. Among infants with intrauterine growth retardation, gestational age was not independently associated with proportionality (in particular, late term and post-term infants did not tend to be more disproportional), a finding that does not support the hypothesis that earlier onset of growth retardation leads to more proportional growth retardation. The results raise serious questions about previous studies of proportionality, particularly those suggesting a nutritional etiology for proportional intrauterine growth retardation.(ABSTRACT TRUNCATED AT 250 WORDS)     

极早产儿产房复苏插管影响因素分析

目的 探讨极早产儿产房复苏插管影响因素以降低插管风险.方法 回顾性分析2017年1月至2019年12月入住新生儿重症监护病房的极早产儿455例,依据复苏时是否插管分为插管组(79例)和非插管组(376例),分析复苏插管的影响因素.结果 极早产儿中复苏时插管发生率为17.4％(79/455).非插管组胎龄、出生体重及剖宫...     

Neurology and behaviour of growth-retarded neonates. Relation to biochemical placental function tests in late pregnancy

Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were done in a prospective study on 29 pregnancies in which intrauterine growth retardation was diagnosed in the third trimester by the gravidogram method and/or serial ultrasound measurements of the fetal biparietal diameter. The series was divided into 2 growth-retarded groups: (i) severe growth retardation with birth weight less than -2 SD from the mean for gestational age (N = 14); (ii) moderate growth retardation with birth weight between -1 and -2 SD from the mean for gestational age (N = 15). These were compared with a control group of 18 normal pregnancies and infants. A modified Prechtl neurological examination and the Brazelton Neonatal Behavioural Assessment Scale (NBAS) were done in the neonatal period at full-term age. Both categories of growth-retarded infants showed lower muscle tonus than the controls. The severely growth-retarded infants showed fewer optimal items in the neurological examination; they also showed poorer capacity for orientation to external stimuli, inferior motor function, and less physiological stability in NBAS than the controls. The abnormal biochemical placental tests were significantly correlated to low Apgar scores (urinary oestriol), to low excitability (S-CAP) and to poor motor function (S-HCS). The neurological and behavioural condition of the neonate seemed to be more closely associated to the extent of growth retardation than to the occurrence of abnormal biochemical placental tests.     

Preterm infants' early developmental status is associated with later developmental outcome

Aim: To assess the development of preterm infants from 40 weeks gestational age to 18 months corrected age to identify early predictors of later development. Methods: Fifty‐one infants were involved. Infant development was assessed at 40 and 44 weeks gestational age with the Brazelton neonatal behavioral assessment scale and a self‐regulation scale and at 3, 6, 10, 18 months corrected age with the Bayley Scales of Infant Development. The quality of general movements was assessed at 1 and 3 months corrected age and maternal attachment style at infant’s age of 6 months corrected age with the Relation Scale Questionnaire. Results: At term age and 1‐month corrected age, preterm infants were less mature and had lower levels of self‐regulation than full‐term infants. At 3 months corrected age, a higher proportion of preterm infants (43%) had mildly abnormal motor quality compared to the general population (25%). At all follow‐ups, preterm infants had delayed mental, motor and behavioural development, which was associated with the level of self‐regulation, motor quality and maternal attachment style. Maternal education level was the most predominant background factor related to infant development. Conclusion: Preterm infants show early‐in‐life deviations in self‐regulation, motor quality and development. These deviations are risk factors for later optimal functioning.     

Intrauterine growth restriction affects the preterm infant's hippocampus

The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency.     

The effect of abnormal intrauterine thyroid hormone economies on infant cognitive abilities

OBJECTIVE: To evaluate how intrauterine and neonatal thyroid hormone deficiencies affect infant cognitive abilities. METHOD: 26 infants with intrauterine or neonatal thyroid hormone deficiency and 20 full-term infants with normal thyroid economies were studied at 6 months of age or corrected age. Reasons for thyroid hormone deficiency were maternal hypothyroidism, maternal hyperthyroidism treated with antithyroid medication, congenital hypothyroidism, and low-risk prematurity. A computer-generated task during which infants' eye-movements were videotaped was used to assess attention, memory, and learning abilities RESULTS: Data from transcribed videotapes showed the study group was significantly less attentive and had longer reaction times than controls but did not differ on indices of sustaining attention or learning. Within thyroid-deficient groups, offspring of treated hyperthyroid mothers showed an atypical profile suggestive of hypervigilance. CONCLUSION: A decreased fetal or maternal thyroid hormone supply in pregnancy is associated with infants' poorer attention and altered rates of information processing.     

Placental histopathology in the extremely low birth weight infants

Our objective was to evaluate the placental histopathology (PH) in extremely low birth weight infants (ELBW, birth weight < 1000 g) and to determine if placental histopathological findings are associated with neonatal mortality in them. The PH of all ELBW infants (gestational age 23-30 weeks) born during a 3-year study period was prospectively evaluated and compared with term infants (gestational age > or = 37 weeks). Additionally PH of ELBW infants who expired within 28 days of life was compared with those who survived beyond 28 days. Student's t test, chi(2) test and Pearson's correlation coefficient tests were utilized for data analysis. The occurrences of placental infection (chorioamnionitis, HCA), umbilical cord inflammation (funisitis, vasculitis, and subacute necrotizing funisitis, analyzed collectively as HFV), and abruption were higher in ELBW (n = 105) compared to term infants (n = 61, p = 0.001, 0.0002, and 0.0002, respectively). Placental findings did not differ between the surviving (n = 71) and nonsurviving (n = 51) ELBW infants. Birth weight and gestational age were higher in the surviving group (p = 0.003 and 0.001, respectively). Placental abruption was found more commonly in the presence of HCA and HFV in ELBW infants as opposed to maternal hypertension in term infants. All ELBW placentas with HFV had concomitant findings of HCA whereas only 42% of ELBW placentas with HCA had findings of HFV compared to 24% in term infants (p = 0.09). There was a weak inverse correlation between HCA and birth weight in all (r = - 0.3, p = 0.01) but not in ELBW infants (r = 0.2, p = 0.07). We conclude that placental and umbilical cord inflammation and placental abruption are more commonly present in ELBW compared to term infants. However, these findings do not contribute to neonatal mortality in ELBW infants. Forty-two percent of placental (maternal) inflammation cases have concomitant cord (fetal) inflammation in ELBW infants. Finally HCA correlates inversely with birth weight in neonates.     

Outcome in infants born to mothers with unexplained elevations of maternal serum alpha-fetoprotein

The outcome in infants without fetal neural tube defect born to mothers with elevated maternal serum alpha-fetoprotein was studied. Elevated maternal serum alpha-fetoprotein with normal amniotic fluid alpha-fetoprotein was found to be associated with an increased incidence of intrauterine growth retardation and nonneural tube congenital anomalies. There was no increased incidence of developmental disabilities in infants born to mothers with elevated maternal serum alpha-fetoprotein. It is speculated that adverse events occurring early in gestation may simultaneously result in congenital anomalies and subsequently elevated maternal serum alpha-fetoprotein, perhaps through disruption of the normal placental barrier between the fetal and maternal circulations.     

New insights into the development of retinopathy of prematurity – importance of early weight gain

Evidence is accumulating that one of the strongest predictors of retinopathy of prematurity (ROP), in addition to low gestational age, is poor weight gain during the first weeks of life. In infants born preterm, the retina is not fully vascularised. The more premature the child, the larger is the avascular area. In response to hypoxia, vascular endothelial growth factor (VEGF) is secreted. For appropriate VEGF‐induced vessel growth, sufficient levels of insulin‐like growth factor I (IGF‐I) in serum are necessary. IGF‐I is a peptide, related to nutrition supply, which is essential for both pre‐ and post‐natal general growth as well as for growth of the retinal vasculature. In prematurely born infants, serum levels are closely related to gestational age and are lower in more prematurely born infants. At preterm birth the placental supply of nutrients is lost, growth factors are suddenly reduced and general as well as vascular growth slows down or ceases. In addition, the relative hyperoxia of the extra‐uterine milieu, together with supplemental oxygen, causes a regression of already developed retinal vessels. Postnatal growth retardation is a major problem in very preterm infants. Both poor early weight gain and low serum levels of IGF‐I during the first weeks/months of life have been found to be correlated with severity of ROP. Conclusion: This review will focus on the mechanisms leading to ROP by exploring factors responsible for poor early weight gain and abnormal vascularisation of the eye of the preterm infant.     

早产儿喂养不耐受的危险因素分析

目的 探讨早产儿发生喂养不耐受(FI)的危险因素.方法 对112例早产儿进行回顾性调查分析.以母体异常、羊水异常、脐带异常、胎盘异常、胎膜早破、胎龄、出生体质量、围生期感染、新生儿高胆红素血症、分娩方式等17个高危因素进行单因素分析,采用Logistic回归分析各个危险因素与早产儿发生FI的相关性.结果 112例早产儿中53例发生FI,发生率为47.32%.经单因素分析显示FI组产前因素中分娩方式、胎膜早破、羊水异常、脐带异常,出生后因素中高胆红素血症、贫血、使用肺表面活性物质与无相关因素早产儿比较均无统计学差异.多因素Logistic回归分析显示:宫内窘迫、胎盘异常和围生期感染是FI发病的危险因素;胎龄、产前使用糖皮质激素是发生FI的保护因素.结论 早产儿出生胎龄越小,发生FI的概率越高,产前使用糖皮质激素可减少FI发生,存在宫内窘迫、胎盘异常和围生期感染的早产儿易发生FI,在建立胃肠营养时要区别对待.     

Increased leptin concentration in preterm infants of pre-eclamptic mothers

AIM: To study the effect of maternal pre-eclampsia on cord plasma leptin concentrations in preterm infants. METHODS: Leptin concentration was analysed in cord plasma of 74 preterm infants, gestational age 24 to 32 weeks. Of these, 14 were born to pre-eclamptic mothers, in 10 intrauterine growth retardation (IUGR) was present, and 59 had been exposed antenatally to corticosteroids. RESULTS: The mean (SD) concentration of cord plasma leptin was 1.31 (0.88) microg/l. A significant correlation was found between leptin concentration and gestational age (r = 0.336; p = 0.0037). Leptin levels were higher in infants of pre-eclamptic mothers (p = 0.0007), in those with IUGR (p = 0.0005), and in infants exposed antenatally to corticosteroids (p = 0.02). In multiple regression analysis, leptin was associated with gestational age and maternal pre-eclampsia (both p < 0.05), but not with antenatal corticosteroids. CONCLUSIONS: Increased fetal leptin in maternal pre-eclampsia may reflect a physiological adaptation to fetal stress such as hypoxia.     

Resistance to thyroid hormone and its molecular basis

Generalized resistance to thyroid hormone (GRTH) is an inherited syndrome characterized by hyposensitivity of target tissues to thyroid hormone. The clinical presentation is variable. The syndrome is usually suspected when elevated serum thyroid hormone levels are associated with a non-suppressed thyroid-stimulating hormone (TSH). While goiter and thyroid test abnormalities have more often led to the suspicion of thyroid gland dysfunction, short stature, hyperactivity, learning disability and goiter in children or adolescents and recalcitrant goiter in adults, should raise the suspicion of GRTH. Hypothyroidism has been considered when growth or mental retardation was the presenting symptom and thyrotoxicosis when confronted with attention deficit, hyperactivity or tachycardia. Failure to recognize the inappropriate persistence of TSH secretion in spite of elevated thyroid hormone levels has commonly resulted in erroneous diagnosis leading to antithyroid treatment. More than 300 subjects with this syndrome have been identified. The mode of inheritance in the majority of families is autosomal dominant. Recessive transmission has been found in only one family. It has long been speculated that this defect is likely to be caused by an abnormal thyroid hormone receptor (TR), but this hypothesis could not be directly tested until the isolation of two TR genes, TRα and TRβ. Mutations in the TRβ gene have been identified in 42 families with GRTH. All are located in the T₃-binding domain straddling the putative dimerization region and exhibit various degrees of hormone-binding impairment. This finding, and the fact that heterozygous subjects with complete TR deletion are not affected while those with point mutations are, indicates that interactions of a mutant TR with normal TR and with other factors are responsible for the dominant inheritance of GRTH and its heterogeneity. Elucidation of the etiology of GRTH has not only added a new means for the early diagnosis of the syndrome but provided new insights in the understanding of the mechanism of hormone action.