Neurodevelopmental outcome at early school age of children born to mothers with gestational diabetes.

AIMS: To study the metabolic derangements in the second half of pregnancy caused by gestational diabetes, on the long term development of children. METHODS: The neuropsychological function of 32 school age children born to 32 mothers with well controlled gestational diabetes and 57 control children matched by age, birth order, and parental socioeconomic status was studied. RESULTS: There were no differences in head circumference and height, but the children born to diabetic mothers were heavier. The verbal IQ scores of index children below the age of 9 years were lower than those of control children. No differences were found between the groups in various sensory and motor functions and in the Touwen and Prechtl neurological test. The young index group children performed less well than controls in fine and gross motor functions, as observed on the Bruininks-Oseretzky test of motor proficiency. The scores of young children born to mothers with gestational diabetes were also lower than controls on the Pollack tapper test, and there were more index group children who scored abnormally on the parents' Conners questionnaire. No correlation was found between the performance of the index group children on various neurodevelopmental tests and the severity of perinatal complications. The differences tended to disappear with age. CONCLUSIONS: Gestational diabetes, as a result of the metabolic abnormalities in the second half of pregnancy, induces long term minor neurological deficits which are more pronounced in younger children. There does not seem to be any direct relation between the appearance of congenital anomalies and neurodevelopmental outcome.     

Neurological findings at follow-up in neonatal hypoglycaemia.

Follow-up examination was carried out in 37 children who had been hypoglycaemic during the neonatal period. Mean age was 3 1/2 years. Five out of 7 children with asymptomatic hypoglycaemia neonatally were completely normal, while minimal brain dysfunction was evident in one, and another child showed pathological EEG. Symptomatic, transient hypoglycaemia seemed to carry a poor prognosis as only one out of 9 individuals was normal. Four patients in this group had convulsions after the neonatal period; two of these had recurrence of hypoglycaemia. One had infantile spasms and was severely mentally retarded with spastic diplegia and epilepsy. One girl was blind due to optic nerve atrophy. Four cases of cerebral palsy were detected in this group. Among 21 cases of secondary hypoglycaemia there were no cases of serious neurological sequelae. It is reasonable to assume that neonatal hypoglycaemia is an important prognostic factor. The deleterious effect on the CNS seems to be related to the duration and severity of the hypoglycaemia.     

NEUROLOGICAL FINDINGS AT FOLLOW-UP IN NEONATAL HYPOGLYCAEMIA

ABSTRACT: Fluge, G. (Department of Paediatrics, University of Bergen, Bergen, Norway). Neurological findings at follow-up in neonatal hypoglycaemia. Acta Paediatr Scand, 64:629, 1975.–Follow-up examination was carried out in 37 children who had been hypoglycaemic during the neonatal period. Mean age was 3 1/2 years. Five out of 7 children with asymptomatic hypoglycaemia neonatally were completely normal, while minimal brain dysfunction was evident in one, and another child showed pathological EEC Symptomatic, transient hypoglycaemia seemed to carry a poor prognosis as only one out of 9 individuals was normal. Four patients in this group had convulsions after the neonatal period; two of these had recurrence of hypoglycaemia. One had infantile spasms and was severely mentally retarded with spastic diplegia and epilepsy. One girl was blind due to optic nerve atrophy. Four cases of cerebral palsy were detected in this group. Among 21 cases of secondary hypoglycaemia there were no cases of serious neurological sequelae. It is reasonable to assume that neonatal hypoglycaemia is an important prognostic factor. The deleterious effect on the CNS seems to be related to the duration and severity of the hypoglycaemia.     

Neurobehaviour of school age children born to diabetic mothers

AIM—To study the neurobehavioural effects that diabetes during pregnancy might have on children by school age.METHODS—The neurobehavioural function of 57 school age children born to 48, well controlled diabetic mothers was compared with 57control children matched for age, birth order, and parental socioeconomic status, using several cognitive, behavioural, sensory and motor neurological tests.RESULTS—The IQ scores of the index group children were similar to those of control children (117.7±13.4 vs 118.5±10.1). There were no differences between the groups in various sensory motor functions. However, the index group children performed less well than the controls on indices of fine and gross motor functions, as observed on the Bruininks-Oseretzky test of motor proficiency. The scores of children born to diabetic mothers were higher than controls on the Touwen and Prechtl neurological examination. They also performed worse in the Pollack tapper test which is designed to detect minor neurological deficits, inattention, and hyperactivity. The index children had higher scores on the Conners abbreviated parent-teacher questionnaire which measures hyperactivity and inattention. There was a negative correlation between the performance of the index group children on various neurodevelopmental and behavioural tests and the severity of hyperglycaemia, as assessed by blood glycosylated haemoglobin and acetonuria.CONCLUSIONS—Diabetes during pregnancy adversely affects some fine neurological functions in children at school age, but not their cognitive scores. These effects are not correlated with the degree of glycaemic control.     

Ultrasound findings and clinical antecedents of cerebral palsy in very preterm infants.

OBJECTIVE: To investigate the incidence and timing of neonatal ultrasound lesions, and clinical details about pregnancy and the perinatal period, in a total population of extremely premature children with cerebral palsy, born to mothers who were resident in Oxfordshire. METHODS: Eighteen children born at less than 32 completed weeks of gestation were identified from a regional cerebral palsy register. Eighteen controls were matched for gestation, time, and place of birth. Perinatal records and ultrasound reports were systematically reviewed. Sequential neonatal ultrasound images stored on videotape were reanalysed, blind to the outcome of the infants. RESULTS: Sixteen (89%) of the cerebral palsy cases and one (6%) control had parenchymal cysts on neonatal brain scans. Of the cerebral palsy cases, none had cysts detectable on the first day. Six developed cysts within the first 10 days of life, and two of these had periventricular echodensities when first scanned postnatally. Antenatal complications were recorded in 16 cases and nine controls. The early postnatal appearance of cysts in a few babies with a history of severe antenatal complications suggested that antenatal factors may have contributed to the cerebral pathology. CONCLUSIONS: Intrauterine factors may have contributed to adverse neurological outcome, but 16/18 of the preterm cerebral palsy cases had an associated cerebral lesion which developed in the perinatal period.     

Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes

Diabetes during pregnancy may be associated with a high rate of congenital anomalies, disturbances of intrauterine growth and often post-natal neurobehavioral abnormalities in the offspring. The latter are associated with pregestational (PGD) as well as with gestational diabetes (GD). In this review we discuss the effects of maternal glucose intolerance on the long-term growth and development of the offspring. In well-controlled diabetes, birth weight is often within normal limits while in partially controlled diabetes newborns are often macrosomic. In PGD mothers with nephropathy, newborns tend to be born prematurely and small for gestational age (SGA). Offspring of diabetic mothers are often large and overweight in comparison to controls. Their long-term development is sometimes impaired. Delayed brain maturity is often observed in newborns of diabetic mothers compared to controls. The IQ scores of the children born to well controlled diabetic mothers are generally similar to that of control children. However, these children perform less well than controls in fine and gross motor functions. They also seem to have a higher rate of inattention and/or hyperactivity as observed by various tests and questionnaires. In our studies we found, in accordance with published literature, a negative correlation between the performance of the children born to mothers with PGD or GD on various neurodevelopmental and behavioral tests and the severity of maternal hyperglycemia as assessed by blood glycosylated hemoglobin levels and acetonuria. In conclusion: PGD or GD may adversely affect intrauterine and postnatal growth, attention span and motor functions of the offspring, but not their cognitive ability unless complicated by nephropathy or hypertension. These effects are negatively correlated with the degree of maternal glycemic control.     

Comparison of the motor development of school-age children born to mothers with and without diabetes mellitus

The objectives of this study were to examine the effects of diabetes during pregnancy on the long-term motor development of the offspring and to study possible correlations between glycemic control and motor development. We compared the motor development of 57 children, 5- to 12-years-of-age, born to 48 mothers with well-controlled diabetes, to the motor development of 57 control children matched by age, birth order, and parental socio-economic status. Children born to mothers with diabetes performed less well than controls in fine and gross motor functions on the Bruininks-Oseretsky Test of Motor Proficiency. A negative correlation existed between the test scores of the children whose mothers had diabetes and the severity of hyperglycemia as assessed by blood glycosylated hemoglobin levels and acetonuria. Motor ability of the children of mothers with diabetes had a high correlation with biological and environmental variables. These results suggest that diabetes during pregnancy may affect the developing brain, inducing long-term mild motor deficiency. The effects seem to result from the adverse effects of diabetic metabolic factors, and the effects correlate with the degree of diabetes control. The combination of metabolic functioning of women with diabetes and home environment may affect the motor development of their children.     

Research priorities in diabetic pregnancy today: the role of animal models

Strict metabolic control has resulted in a striking fall in the rates for stillbirths, neonatal deaths and neonatal morbidity in diabetic pregnancy. However, clinical problems and challenges for research remain, particularly in relation to a high incidence of congenital malformation, low birth weight, and early growth delay; the detection and management of gestational diabetes; insulin delivery systems; the consequences of maternal hypoglycaemia on organogenesis and fetal well-being; the mechanisms underlying various categories of neonatal morbidity, and possible long-term morbidity in the children born to diabetic mothers. The nature of these problems determines that certain fundamental aspects of reproduction which are difficult to study in human pregnancy will have high priority for research. Progress in this field will be heavily dependent on animal models in the foreseeable future.     

Neontal hypoglycaemia in infants of insulin-dependent diabetic mothers.

Neonatal hypoglycaemia (blood glucose smaller than 20 mg/100 ml) occurred in the first 6 hours of life in 25 of 34 infants born to diabetic mothers receiving insulin. Despite severe hypoglycaemia (blood glucose smaller than 10 mg/100 ml) in 17, clinical features of hypoglycaemia were absent in all but 2. Hypoglycaemia was not related either to the level of plasma insulin in cord blood, determined as nonextracted immunoreactive insulin, or to the degree of control of maternal blood glucose during pregnancy. The frequent occurrence of severe neonatal hypoglycaemia in the infants born to diabetic mothers receiving insulin appears to be due rather to failure to maintain basal glucose homoeostasis after birth than to hyperinsulinism.     

Cerebral palsy and neonatal encephalopathy.

A retrospective cohort study was carried out to test the hypothesis that children born at term with cerebral palsy with signs of neurological dysfunction preceded by depression at birth (termed neonatal encephalopathy) differ from those without such signs in the frequency of antenatal and perinatal factors, and in the severity and characteristics of their impairment and disability. The study was carried out in the area covered by Oxford Regional Health Authority. Antenatal, intrapartum, neonatal factors, and the later clinical status of the two groups of children were used as the main outcome measures. Although most maternal and antenatal characteristics were similar in the two groups, the mothers of children with a history of neonatal encephalopathy were more likely to be primigravidae (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.0 to 4.3) and to have a pregnancy of greater than 41 weeks' gestation (OR 3.5; 95% CI 1.0 to 12.1). Intrapartum complications were more frequent in the neonatal encephalopathy group: meconium staining of the amniotic fluid (OR 3.5; 95% CI 1.5 to 7.8), an ominous first stage cardiotocograph (OR 10.2; 95% CI 2.9 to 36.4), with a longer median duration of abnormality (200 v 48 minutes). At 5 years of age those with neonatal encephalopathy were more likely to have developed spastic quadriplegia (OR 4.8; 95% CI 2.2 to 10.5), to have visual impairment (OR 3.0; 95% CI 1.0 to 8.6), and to be non-walking (OR 4.0; 95% CI 1.8 to 8.8) than those without neonatal encephalopathy. Children with cerebral palsy who were born at term and have neonatal encephalopathy are more likely to have had signs of intrapartum asphyxia and are more likely to have a more severe form of cerebral palsy than those without a history of neonatal encephalopathy. Although this group represents only one in 10 of all cases of cerebral palsy, some of these may be obstetrically preventable.     

Neonatal morbidity and mortality associated with maternal HELLP syndrome

The syndrome of hemolysis, elevated liver enzymes and low platelet count (HELLP syndrome) is a severe form of preeclampsia and eclampsia. To compare the impact of HELLP syndrome and hypertension in pregnancy (HIP) on neonatal morbidity and mortality, 11 infants born to mothers with HELLP syndrome were recruited between 1993 and 1997 from neonatal records. They were compared to 11 infants born to mothers with HIP and 11 control infants born to healthy mothers matched for gestational age, postnatal age and gender. Cesarean section rate was higher in the HELLP group than in the controls (p < 0.05). HELLP group infants had lower Apgar scores (54.5% < 1 at 5th min), than controls (9.1%) (p < 0.05). Both HELLP and HIP group infants showed a higher incidence of intrauterine growth retardation (63.6% and 54.5%, respectively) than the controls (9.1%) (p < 0.05). The incidence of respiratory distress syndrome (RDS) was similar in HELLP and HIP groups and was greater than that in controls (p = NS). Additionally, the neonatal death rate was the highest in the HELLP group (p = NS).     

A fifteen-year follow-up of neurological conditions in VLBW children without overt disability: relation to gender, neonatal risk factors, and end stage MRI findings

BACKGROUND: Very low birthweight (VLBW; birthweight 相似文献   

Neurodevelopmental outcome of hypoglycaemia in healthy, large for gestational age, term newborns

AIMS: To evaluate the effects of transient hypoglycaemia on the first day of life in 75 healthy term large for gestational age (LGA) infants, born to non-diabetic mothers, on their neurodevelopmental outcome at the age of 4 years. METHODS: Screening for hypoglycaemia was performed 1, 3, and 5 hours after birth, and continued if blood glucose levels were low. Treatment with intravenous glucose for hypoglycaemia was started if hypoglycaemia was severe or symptomatic. Patients' development and behaviour was examined at the age of 4 years by the Denver Developmental Scale, a non-verbal intelligence test, and the Child Behaviour Check List. RESULTS: There were no significant differences between children with neonatal normoglycaemia (n = 15) and hypoglycaemia (plasma glucose <2.2 mmol/l 1 hour after birth, or <2.5 mmol/l subsequently; n = 60) in Denver developmental scale scores and child behaviour checklist scores. Although total IQ did not differ between hypoglycaemic and normoglycaemic children, one subscale (reasoning) did (mean difference 9.3, 95% CI 1.3 to 17.2). The correlation between reasoning IQ and neonatal blood glucose levels was weak and not statistically significant. When other definitions for hypoglycaemia were applied, the difference in reasoning IQ was not found. There were no differences in any of the test scores between hypoglycaemic children who had and who had not been treated with intravenous glucose. CONCLUSION: Transient mild hypoglycaemia in healthy, term LGA newborns does not appear to be harmful to psychomotor development at the age of 4 years.     

Neonatal behavior after drug dependent pregnancy.

Neurobehavioural development of 35 infants of drug dependent mothers was compared with the development of 37 reference infants as part of a prospective longitudinal research project. Infants of drug dependent mothers had more poor responses than the other children on neurological examination. This difference is significant only when data of infants of drug dependent mothers born at full term are analysed. Two tailed testing indicated that significantly more infants of drug dependent mothers than reference children had electro-encephalograms rated as suspect or abnormal. By the end of the first month the infants of drug dependent mothers tended to be more active, and they had worse scores than the reference children on the neonatal behavioural assessment scale. Analysing data only of infants born at full term, the groups differ significantly on the interactive items. The results of this study show that even after treatment for the neonatal abstinence syndrome, infants of drug dependent mothers seem to differ from comparison children, which could indicate later developmental problems.     

Morbidity and neurological function of very low birthweight infants from the newborn period to 4y of age. A prospective study from the south-east region of Sweden

All 107 infants weighing ≤1500 g at birth (VLBW) and born alive in the south-east region of Sweden during a 15-month period in 1987-88 were enrolled in a prospective study to determine the prevalence of handicap and to assess neurological function in comparison with controls. Eighty-six (80%) infants survived. Twenty (19%) had intracranial haemorrhages (ICH) assessed by ultrasound examinations in the neonatal period and 2 (2.3%) retinopathy of prematurity stage 3 or more. The VLBW infants who survived had fewer optimal neurological responses than the controls at 40 weeks post-conceptional age. Eighty-two VLBW children were followed to 4y of age. Three (4%) children had a neurological handicap and 9 (11%) had a moderate neurological deviation. Neither the size of ICH nor neonatal optimality score correlated to neurological outcome at 4 y of age. The VLBW children without neurological handicap or deviation (n = 70) had a delay in psychomotor development in comparison with the controls. Mental development and school performance, in particular language development, will be examined at school age.     

Minimal brain dysfunction in preschool age--risk for trouble in school?

In general health examinations of 2,447 4-year-old children in a certain area of southern Sweden, comprising 95.1% of the total population of that age, 52 children (2.1%) were diagnosed as having minimal brain dysfunction. After 7--9 years the children were reexamined and their parents and teachers were interviewed. Although no specific treatment, like stimulant drugs, was given, the children were much improved as they grew older: their hyperactivity had diminished, their behavior did not cause as much trouble, and their remaining neurological disturbances were small. However, the children manifested more problems in elementary school than other children, both regarding behavior, learning, slight neurological disturbances and visual disorders. Thus, the small group of children with minimal brain dysfunction symptoms in preschool age seem to run a certain risk of having trouble in school, although the symptoms are less conspicious as they grow and mature.     

Population-based case-control study of mebendazole in pregnant women for birth outcomes

The objectives of the study was to check the embryotoxic-teratogenic and fetotoxic effect of mebendazole (Vermox; Richter, Budapest, Hungary) treatment during pregnancy. Mebendazole use during pregnancy was evaluated in mothers of babies born with congenital abnormalities and in matched control mothers of babies born without congenital abnormalities in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 22,843 women who had newborns or fetuses with congenital abnormalities, 14 were found to have been treated with mebendazole for intestinal nematoda infections/diseases during pregnancy (crude POR: 1.8 with 95% CI: 0.7-4.2). Of 38,151 women who had newborns without any defects (controls), the same number (14) were found to have been treated with mebendazole during pregnancy. Six different congenital abnormality groups were evaluated and a higher prevalence of mebendazole use in these mothers throughout pregnancy was not found. Gestational age and birth weight were analyzed in control infants born to mothers with or without mebendazole treatment. The mean gestational age was somewhat longer and mean birth weight was larger in newborn infants born to mothers with mebendazole treatment. Thus, treatment with mebendazole during pregnancy did not indicate a teratogenic and fetotoxic risk to the embryo or fetus, though the numbers of treated cases and controls in this study were limited.     

Maternal hypertension and neurodevelopmental outcome in very preterm infants

AIM—To determine the outcome of preterm infants born to mothers with hypertension during pregnancy, and preterm controls.
METHODS—107 infants of 24-32 weeks gestation, born to hypertensive mothers, and 107 controls matched for gestational age, sex, and multiple pregnancy, born to normotensive mothers, were prospectively enrolled over 2 years. Information on maternal complications and medication was obtained and neonatal mortality and morbidities recorded. Survivors were followed up to at least 2 years, corrected for prematurity.
RESULTS—One third of the hypertensive mothers were treated with antihypertensive drugs, while 18% received convulsion prophylaxis with phenytoin. Magnesium sulphate was not prescribed. Both groups had a mean gestational age of 29.9 weeks, with the study infants having a significantly lower birthweight than the controls. Four study and three control infants died in the neonatal period. Cerebral palsy was not diagnosed in any infant of a hypertensive mother compared with five of the controls. The mean general quotient for the two groups was very similar and no difference in the incidence of minor neuromotor developmental problems was shown.
CONCLUSIONS—Maternal hypertension seems to protect against cerebral palsy in preterm infants without increasing the risk of cognitive impairment. This was independent of the use of maternally administered magnesium sulphate.

     

CLINICAL ASPECTS OF NEONATAL HYPOGLYCAEMIA

ABSTRACT. Fluge, G. (Department of Paediatrics, University of Bergen, Bergen, Norway). Clinical aspects of neonatal hypoglycaemia. Acta Paediatr Scand, 63: 826, 194.—Fifty cases of neonatal hypoglycaemia were detected by routine blood glucose determination in 323 low birth weight infants during a three-year period (15.4%) and, in addition, hypoglycaemia was diagnosed in 17 full-term infants. The patients were divided in three groups according to clinical findings, with special reference to age at diagnosis, pretreatment blood glucose values and duration of hypoglycaemia. In asymptomatic hypoglycaemia the diagnosis was made during the first few hours after birth, and the mean pretreatment blood glucose value was 14 mg/100 ml. Except for one patient, the hypoglycaemia was of short duration. Symptomatic, transient hypoglycaemia was characterized by a delay in onset of symptoms until the second and third day after birth, low pretreatment blood glucose level and hypoglycaemia of long duration. Hypoglycaemia associated with other neonatal disorders classified as secondary hypoglycaemia usually was noted during the first few hours of life, and tended to he of short duration. Frequency of hypoglycaemia in small for gestational age infants was markedly higher when toxaemia of pregnancy was noted, compared with infants born to non-toxaemic mothers.     

Impact of perinatal COVID on fetal and neonatal brain and neurodevelopmental outcomes

After three years of the COVID-19 pandemic, we have learned many aspects of the disease and the virus: its molecular structure, how it infects human cells, the clinical picture at different ages, potential therapies, and the effectiveness of prophylaxis. Research is currently focused on the short- and long-term consequences of COVID-19. We review the available information on the neurodevelopmental outcome of infants born during the pandemic from infected and non-infected mothers, as well as the neurological impact of neonatal SARS-CoV-2 infection. We also discuss the mechanisms that could potentially affect the fetal or neonatal brain including direct impact after vertical transmission, maternal immune activation with a proinflammatory cytokine storm, and finally the consequences of complications of pregnancy secondary to maternal infection that could affect the fetus. Several follow-up studies have noted a variety of neurodevelopmental sequelae among infants born during the pandemic. There is controversy as to the exact etiopathogenesis of these neurodevelopmental effects: from the infection itself or as a result of parental emotional stress during that period. We summarize case reports of acute neonatal SARS-CoV-2 infections associated with neurological signs and neuroimaging changes. Many infants born during previous pandemics caused by other respiratory viruses demonstrated serious neurodevelopmental and psychological sequelae that were only recognized after several years of follow-up. It is essential to warn health authorities about the need for very long-term continuous follow up of infants born during the SARS-CoV-2 pandemic for early detection and treatment that could help mitigate the neurodevelopmental consequences of perinatal COVID-19.