Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study.

OBJECTIVE: To monitor pregnancies in women with pre-existent insulin dependent diabetes for pregnancy loss, congenital malformations, and fetal growth in a geographically defined area of north west England. DESIGN: Population cohort study. SETTING: 10 maternity units in Cheshire, Lancashire, and Merseyside which had no regional guidelines for the management of pregnancy in diabetic women. SUBJECTS: 462 pregnancies in 355 women with insulin dependent diabetes from the 10 centres over five years (1990-4 inclusive). MAIN OUTCOME MEASURES: Numbers and rates of miscarriages, stillbirths, and neonatal and postneonatal deaths; prevalence of congenital malformations; birth weight in relation to gestational age. RESULTS: Among 462 pregnancies, 351 (76%) resulted in a liveborn infant, 78 (17%) aborted spontaneously, nine (2%) resulted in stillbirth, and 24 (5%) were terminated. Of the terminations, nine were for congenital malformation. The stillbirth rate was 25.0/1000 total births (95% confidence interval 8.9 to 41.1) compared with a population rate of 5.0/1000, and infant mortality was 19.9/1000 live births (5.3 to 34.6) compared with 6.8/1000. The prevalence of congenital malformations was 94.0/1000 live births (63.5 to 124.5) compared with 9.7/1000 in the general population. When corrected for gestational age, mean birth weight in the sample was 1.3 standard deviations greater than that of infants of non-diabetic mothers. Infants with congenital malformations weighed less than those without. CONCLUSION: In an unselected population the infants of women with pre-existent insulin dependent diabetes mellitus have a 10-fold greater risk of a congenital malformation and a fivefold greater risk of being stillborn than infants in the general population. Further improvements in the management of pregnancy in diabetic women are needed if target of the St Vincent declaration of 1989 is to be met.     

ACP1 and human adaptability 2. Association with season of conception

We have studied the pattern of association between the season of conception and cytosolic low molecular weight phosphotyrosine phosphatase (ACP1) genetic polymorphism in 329 consecutively newborn infants from the population of Penne and 361 consecutively newborn infants from the population of Rome. In addition, 329 mothers were studied in the population of Penne. A concordant, highly significant association was observed in the two populations between ACP1 parameters and the season of conception of newborn infants. The total activity of ACP1 shows a minimum in infants conceived in January–February and a maximum in those conceived at the end of the solar year. Analysis of the joint mother-newborn ACP1 distribution in relation to the season of fertilisation has shown that among mothers carrying ACP1*A (the allele showing the lowest activity), the proportion of newborns carrying this allele is higher in those conceived in the first months of the year than in those conceived subsequently. Since ACP1 probably functions as a phosphotyrosine phosphatase and as a flavin mononucleotide phosphatase, low activity could enhance the metabolic rate and would be advantageous in a cold environment. The cycle of variation of ACP1 in infants follows the cycle of solar illumination. It is possible that individuals who have a genetic background allowing them to adapt easily and readily to seasonal demand are more successful in reproducing themselves. The population of zygotes conceived in a given season would therefore reproduce the pattern of gene combination more fit for that season. Received: 15 June 1997 / Accepted: 31 July 1997     

Neonatal screening in Vancouver for congenital dislocation of the hip.

After 20 years'' experience throughout the Western world the effectiveness of screening newborns for congenital dislocation of the hip remains controversial. Is the clinical test for hip instability (the Ortolani or "jump" sing) reliable? Are other equally important physical signs frequently missed by inexperienced examiners? Do some dislocations develop after the newborn period when no abnormality was identifiable during the first week of life? In Vancouver, screening for this condition was initiated in 1964. In the 5-year period 1967-1971 an orthopedic surgeon screened all the infants in the newborn nursery of one hospital, while orthopedic residents screened all those at another hospital. Their rates of neonatal and late (after the first month of lfe) diagnosis of congenital hip abnormalities were, respectively, 6 and 0.3/100 lives births for the surgeon and 5 and 0.8/1000 for the residents. In contrast, at 20 hospitals that did not have regular screenign the average rates were 1.2 and 1.4. Systematic screening the early treatment have great potential for reducing the need for immobilization and surgical treatment of infants who congenital dislocation of the hip is missed in the first month of life. it may also prevent the arthritic sequelae that in adult life afflict many patients whose treatment was begun after the newborn period.     

Cytogenetic analysis of the noxious bloodsucker Boophthora erythrocephala (Diptera: Simuliidae) from different geographic zones

Boophthora erythrocephala is a widely spread species inhabiting both small polluted water-bodies and large rivers. Three populations from Samara region in Russia and from Donetsk and Chernigov regions in the Ukraine have been studied. Five populations of this species in Russia were described earlier (Polyanskaya, Tsapygina, 1968; Petrukhina, 1972). For identification of this species the chromosome map of Adler and Werner (personal communication) was used. Comparison of 8 populations studied was performed. All of them belong to the species B. erythrocephala but everyone has its own individual characteristics. Inversion polymorphism was observed in each population comprising from 88 to 100 %. Mean number of heterozygous inversions per individual is low fluctuating around 3.6. There is one inversion in IIS observed in all populations that proves panmixy among them. Other inversions occur in a part of the individuals.     

Prospective population based survey of outcome of pregnancy in diabetic women: results of the Northern Diabetic Pregnancy Audit, 1994.

OBJECTIVE: To determine whether the St Vincent declaration (1989) target of diabetic pregnancy outcome approximating non-diabetic pregnancy outcome in near to being achieved. DESIGN: Prospective collection of population based information on pregnancies in women with diabetes from all participating hospitals. SETTING: District general and teaching hospitals of the former Northern region. SUBJECTS: 111 diabetic women booking with pregnancy during 1 January to 31 December 1994. MAIN OUTCOME MEASURES: Diabetic control, perinatal mortality rate, fetal abnormality rate. RESULTS: The perinatal mortality rate was 48/1000 for diabetic pregnancies compared with 8.9/1000 for the background population (odds ratio 5.38; 95% confidence interval 2.27 to 12.70) and the neonatal mortality rate was 59/1000 compared with 3.9/1000 (15.0; 6.77 to 33.10). Two late neonatal deaths were due to congenital heart defects. Six per cent of all fetal losses (6/109 cases) were due to major malformations. The congenital malformation rate was 83/1000 compared with 21.3/1000 (3.76; 2.00 to 7.06) in the background population. CONCLUSIONS: Diabetic pregnancy remains a high risk state with perinatal mortality and fetal malformation rates much higher than in the background population.     

Chromosome anomalies of infants dying during the perinatal period and premature newborn

Summary 363 samples of different tissues were taken for cultivation from 118 antepartum deaths, 85 intrapartum deaths and 112 newborn dying during the first days after delivery. Successful growth of culture was noticed in 48.2% (15.4%) of antepartum deaths; 71.8% of intrapartum deaths and 68.1% of newborn dying during the first days of life. Among the 22 antepartum deaths 3 (13.6%) infants were found to have anomalies of karyotype; among 61 intrapartum deaths 3 (4.9%) infants were found to have karyotype anomalies; and among 92 early neonatal deaths 6 ones (6.5%) had karyotype anomalies. The total frequency of chromosome anomalies among the infants dying during the perinatal period was 6.9%.The final result of cytogenetic investigation of 607 premature infants was that chromosome anomalies were found among 2.5%, that is 3.5 times as much, as in the general newborn population. Among the types of chromosome anomalies the main defects were anomalies in the system of sex chromosomes and trisomy-21, and that is the proof of the fact, that other types of anomalies, found in newborn populations lead to earlier lethality.     

IgG and IgM western blot assay for diagnosis of congenital toxoplasmosis

The aim of this study was to evaluate the utility of western blot (WB) analysis as a diagnostic tool for congenital toxoplasmosis in 215 newborn infants. The children were submitted to clinical examinations to assess macular, neurological and hearing signals. The WB results obtained were compared to the persistence of IgG antibodies at the end of 12 months, which is regarded as the "gold standard" diagnosis of congenital toxoplasmosis. Association between the WB results and the clinical signs presented by the infants was also assessed. Of the 215 children, 177 had a confirmed congenital toxoplasmosis diagnosis and 38 were uninfected. IgG-WB showed a sensitivity of 73.5% and a specificity of 97.4%. IgM-WB showed a sensitivity of 54.8% and a specificity of 94.7%. The IgG-WB and IgM-WB combination increased the sensitivity to 86.5%. The IgM-WB-positive children had a 1.4-fold greater risk of presenting active macular lesions than did those that were IgM-WB-negative. This study showed that the WB assay is a useful tool to confirm a diagnosis of congenital toxoplasmosis and that the IgM-WB-positive results can indicate active macular lesions in newborn infants.     

Necrotizing enterocolitis in neonates with congenital heart disease

Both necrotizing enterocolitis (NEC) and congenital heart disease (CHD) are causes of significant morbidity and mortality in the neonatal population. While two distinct disease processes, NEC and CHD are inter-related as the incidence of NEC is greater in neonates with CHD than the normal newborn population. It is likely that circulatory perturbations, especially those seen in infants with left ventricular outflow tract lesions and single ventricle physiology, the stress of cardiac surgery and cardiopulmonary bypass, and the underlying baseline elevation of circulating endotoxin and proinflammatory cytokines all play a role in the pathogenesis of NEC in this uniquely susceptible population. The neurodevelopmental impairment in infants requiring surgery for NEC and in infants with complex congenital heart disease is alarming and requires further investigation. As medical and surgical advances allow for the palliation and correction of complex lesions at an earlier gestational age and lower birth weight, the already high risk of NEC in this population is likely to increase. This will require more aggressive study of the etiology of NEC in patients with CHD and the development of preventative therapies in order to decrease the impressive morbidity and mortality associated with the combination of these disease processes. In this article, we review the pathogenesis of NEC and CHD including associated mortality and morbidities and discuss possible mechanisms linking these two disease states.     

Genetic demographic processes in Ukrainian population in 1990. The marriage structure of the Donetsk population

Analysis of records of the marriages that were contracted in the city of Donetsk revealed that, between 1960 and 1992, the marriage rate in the city decreased from 14.8 to 4.7 per 1000 people, the migration rate (m) decreased from 0.71 to 0.34, and the endogamy index increased from 0.123 to 0.458. Between 1960 and 1985, outbreeding in the Donetsk population increased, which was expressed in an increase in the frequency of interethnic marriages, migration range, and the average marital distance, as well as a decrease in the proportion of the indigenous ethnic group (Ukrainians). By 1992, outbreeding decreased: the population became more homogeneous ethnically (93% Slavic), the proportion of Ukrainians and the frequency of monoethnic marriages increased, and the average marital distance decreased. In 1960 and 1992, the coefficients of marriage contingency (K) with respect to ethnicity were 0.34 and 0.22, respectively. Regarding birthplaces, the population became almost panmictic (in 1960 and 1992, the K values were 0.15 and 0.10, respectively). Marriage structure with respect to occupation remained almost unchanged (the K values were 0.22 and 0.23, respectively). Throughout the entire period studied, the most pronounced population subdivision was that with respect to the education level (the K values were 0.36 and 0.39, respectively).     

Congenital malformations among newborns and developmental abnormalities among human embryos in Belarus after Chernobyl accident.

Evaluation of the effects of radioactive contamination on human populations is important for an understanding of the present and future risk for human health, including the genetic risk. This review centers on the results of population monitoring of developmental anomalies among human embryos and congenital malformations among newborn in the Republic of Belarus before and after Chemobyl accident. The data revealed that the incidences of developmental anomalies and congenital malformation from the mostly radionuclide-contaminated rural regions of Belarus reliably exceed the indices in control areas.     

Larsen syndrome associated with severe congenital hydrocephalus

Larsen syndrome associated with severe congenital hydrocephalus: Larsen syndrome (LS) is characterized by the association of flattened facies with a prominent forehead, a depressed nasal bridge and hypertelorism, dislocation of hips, elbows and knees, equinovarus or valgus deformities of the feet, long and tapering fingers, normal intelligence. Hydrocephalus has rarely been reported in association with LS. In this article, a newborn infant with the classical features of LS and severe congenital hydrocephalus is presented. Our purpose was to emphasize the importance of congenital hydrocephalus in infants with LS and to highlight the management of cases of LS associated with congenital hydrocephalus.     

Organization and results of mass screening for congenital hypothyroidism in newborn infants in the Cracow province

Screening for congenital hypothyroidism has been carried out in 69,286 newborn children born in the region and city of Krakow in the years 1985-1988. Fourteen cases of congenital thyroid insufficiency were detected indicating the incidence of 1:4816 in this region. In 25 newborns (incidence of 1:1979) a transient hyperthyreotropinemia was diagnosed. It was concluded that the main reason of the appearance of an elevated TSH level in newborns of this region seems to be the deficiency of iodine in the diet and/or environment.     

Neonatal thyroid-stimulating hormone screening as an indirect method for the assessment of iodine deficiency in Estonia

According to neonatal thyroid screening the incidence of congenital hypothyroidism in Estonia is 1:2,860. Transient hyperthyrotropinemia with a raised thyroid-stimulating hormone level of 5 microU/ml occurred in 17.7% of infants and was not associated with low birth weight, small birth length, low gestational age or congenital anomalies. Based on WHO criteria (WHO/UNICEF, 1994) it corresponds to mild iodine deficiency in Estonia (3% or less is in iodine-sufficient areas). This is in agreement with the previously reported median urinary iodine content of 65 microg/l in children. The frequency of infants with TSH >5 microU/ml was 16.4, 21 and 17. 2% in three regions (north, central and south) of Estonia, respectively, indicating mild to moderate iodine deficiency. These findings show the possibility of using the results of newborn screening for congenital hypothyroidism to assess the severity of iodine deficiency in Estonia. The introduction of universal iodine prophylaxis is recommended.     

Prevention and avoidance of congenital malformations

Many congenital abnormalities do not have either a Mendelian pattern of inheritance or an identifiable chromosome abnormality and are described as 'multifactorial' as it is assumed they are determined by several genes, each with added effects and modified to a greater or lesser extent by environmental factors. They include spina bifida and anencephaly, cleft lip or cleft palate or both, congenital heart defect and congenital dislocation of the hip, and they constitute a major community health problem. Developments in genetics, biochemistry and cytogenetics have presented new approaches to the prevention and avoidance of congenital abnormalities. The approaches available for the avoidance of congenital malformations include the avoidance of harmful environmental factors, the screening of the newborn and early treatment, genetic counselling and antenatal monitoring with selective termination. The prevention of neural-tube defects in 'high risk' mothers can be achieved by periconceptional vitamin supplementation. In Northern Ireland, of 438 fully supplemented women, only 4 (0.98%) infants or fetuses among 407 infants and fetuses examined had a neural-tube defect, whereas of 356 unsupplemented women, 16 (4.7%) infants or fetuses among 337 infants or fetuses examined had a neural-tube defect.     

Epidemiology of congenital malformations in Gorno-Altaisk, Altai Republic, Russia

A retrospective epidemiological study has been performed using the data from healthcare institutions of the city of Gorno-Altaisk, Altai Republic, Russia for the period from 1983 to 2001. Congenital malformations (CMFs) have been studied in newborns, infants that died at ages under one year, and fetuses after 22 weeks of gestation. The most frequent malformations are those of the musculoskeletal and cardiovascular systems and multiple malformations, which account for 37.68, 18.22, and 8.9% of all congenital malformations, respectively. Their frequencies are 7.38, 3.57, and 1.74 per thousand, respectively. The frequency of congenital malformations subject to registration by the national system of CMF monitoring of the Russian Federation (21 malformation forms) is 6.08 per 1000 births and varies from 8.59 to 21.24. The frequency of the Down syndrome is 0.93 per 1000 births; it did not vary significantly during the period studied. The frequency of limb reduction deformities in the urban population of Altai Republic (0.32 per 1000 births) is higher than in other Siberian regions, including the cities of Kyzyl (Tyva Republic) and Tomsk and the Nyurba and Ust-Aldan uluses of Sakha Republic (Yakutia).     

Reinfection after rubella and congenital polymalformation syndrome

A case is reported of a term newborn with intra uterine growth retardation and numerous malformations such as complex heart disease, abnormalities of distal limbs, cleft palate. Death occurred after two days. The diagnosis of rubella embryopathy was confirmed by the following criteria: a high level of rubella antibodies in mother and newborn (1/1000) an isolation of rubella virus from the infant's urine. Diagnosis of rubella after reinfection was documented by a high level of antibodies in the mother three years before this pregnancy. Other observations reported in literature confirm the extreme rarity of congenital rubella after reinfection.     

National rates of birth defects among hospitalized newborns

BACKGROUND: The Healthcare Cost and Utilization Project (HCUP) family of hospital discharge databases offer an unprecedented opportunity to generate national estimates of newborn infants with birth defects. This report estimates national hospital admissions for newborn infants diagnosed with birth defects computed from HCUP and compares them to pooled prevalence figures computed from state birth defect surveillance systems. METHODS: HCUP-derived rates of 36 birth defects from 1997 through 2001 were compared to rates derived from pooled data reported by 26 state-based surveillance systems stratified by inclusion of elective terminations in case definitions. Rate ratios (RRs) were calculated for each birth defect by dividing the rate derived from HCUP by the rate derived from the relevant surveillance systems. RESULTS: HCUP newborn hospitalization rates for birth defects closely approximate pooled birth defect rates for surveillance systems that do not include elective terminations. HCUP rates were not significantly different for 35 of 36 defects. Overall, 20 HCUP rates were within 10% of state rates, 11 more were within 20% of state rates, and only 1 differed by more than 50%. HCUP rates compared most closely to state rates for cardiovascular (VSD RR = 0.98, ASD = 0.96, pulmonary valve atresia and stenosis = 0.92), orofacial (cleft palate RR = 1.10, cleft lip = 1.06), and genitourinary defects (obstructive genitourinary RR = 1.01, bladder exstrophy = 0.97). HCUP rates compared less favorably to rates derived from surveillance systems that included elective terminations. CONCLUSIONS: HCUP data approximate state-based surveillance system data for defects that are easily recognized in the newborn period and infrequently a cause for elective termination. HCUP data can be used to examine the impact of public health efforts on the number of infants born with birth defects as well as the cost and consequences of variations in the hospital management of birth defects.     

Congenital defects among liveborn infants with Down syndrome

BACKGROUND: Many infants with Down syndrome (DS) have co-occurring congenital malformations requiring intensive surgical and medical management. To anticipate the care needed by these infants, providers and parents require accurate information about birth defects that may be present. This article uses a unique national hospital discharge dataset to identify the rate at which structural birth defects are identified among liveborn infants with DS. METHODS: ICD-9-CM diagnosis codes for data from the Healthcare Cost and Utilization Project were used to identify infants with and without DS, and to classify birth defects. The study population consisted of liveborn infants discharged from the hospital from 1993 through 2002. ORs for the association between the occurrence of congenital malformations and the presence of DS were computed using logistic regression models for survey data. RESULTS: Discharge data included 11,372 DS and 7,884,209 non-DS births, representing national estimates of 43,463 DS and 39,716,469 non-DS births respectively. In addition to congenital heart defects that co-occurred most often in DS infants compared to infants without DS, the risks for gastrointestinal malformations (OR 67.07), genitourinary malformations (OR 3.62), orofacial malformations (OR 5.63), and abdominal wall malformations (OR 3.25) were also elevated in infants with DS. There was no difference in the risk of spina bifida between infants with and without DS. CONCLUSIONS: This is the first nationally representative compilation of the co-occurrence of congenital malformations associated with DS. This information may assist providers and parents in their attempts to understand and prepare for the true burden of this condition.     

Study of cardiac arrhythmias and other forms of conduction abnormality in newborn infants.

In an unselected population of 2030 newborn infants studied by electrocardiography (ECG) between April 1975 and April 1977, 35 were found to have arrhythmias or other cardiac conduction abnormalities. Further investigation by means of 24-hour ECG monitoring showed that apparently serious tachyarrhythmias, such as ventricular tachycardia and slow heart rates associated with sinoatrial block, may be present without clinical disturbance in some newborn babies. Six infants had both bradycardia and tachycardia in the 24-hour recording, although the screening ECG had shown only one of these abnormalities. The alarming ECG appearance of some of the arrhythmias suggested a possible aetiological link with some unexplained sudden infant deaths: a multicentre study could determine this more readily and is therefore recommended.