Congenital Malformations in Diabetic Pregnancies Clinical Viewpoints

ABSTRACT. A consecutive series of 2 587 newborn infants of diabetic mothers treated during pregnancy and delivery in the period 1926 to 1983 has been analysed. The malformation rate was 6.6%. The series has been divided into five consecutive periods each comprising around 500 infants. During the first four periods the frequency of congenital malformations (CM) was remarkably constant also when related to the severity of the maternal diabetes. During the latest period from 1979 to 1983 a significant decrease in the frequency and severity of CM in infants of diabetic mothers was seen, most marked in the group with more severe maternal diabetes (White's classes D + F). One hundred and thirty-five insulin-dependent diabetic women with regular menstrual histories were examined by ultrasonic scanning in the 7th to 14th week of pregnancy. As judged by the crown-rump length 53 fetuses were smaller than normal. The term early growth delay is used for this phenomenon. Nine of the 135 fetuses had major CM and seven of them were smaller than normal in early pregnancy. These observations show that fetuses that are significantly smaller than normal in early pregnancy carry a higher risk of being malformed and suggest a common mechanism behind early growth delay and induction of abnormal embryogenesis.     

Congenital Malformations and the Environment

Rokicki, W., Latoszkiewicz, K. and Krasnodehski, J. (Department of Paediatric Cardiology, Silesian Medical School, Katowice, Poland). Congenital malformations and the environment. Acta Paediatr Scand Suppl 360: 140, 1989.
The aim of the work was to search for the correlation between the environmental pollution and the ratio of congenital malformations found in the population of 54 493 newborn infants of three Silesian towns: Bielsko-Biala (situated in the mountains, close to a recreation part of the country), Bytom (situated in the center of an old industrial district, where industry is responsible for very high environmental pollution), and Tarnowskie Gory (situated close to vast woodlands, where very high environmental concentration of heavy metals is caused by an outdated, big zinc plant). In spite of big differences of environmental pollution indices between the three towns, the percentage of major congenital malformations diagnosed within the first three days of extrauterine life was almost identical (1.12% in Bielsko-Biala, 1.3% in Bytom, and 1.1 % in Tarnowskie Gory).     

Non-Enzymatic Glycation of Fetal Tissue in Diabetic Pregnancy

ABSTRACT. Non-enzymatic glycation of fetal tissue was studied by determining the glucitollysine content of umbilical cord extracts from twelve infants of diabetic mothers and fourteen infants of healthy, non-diabetic women (controls). The single, glycated amino-acid glycitollysine, which reflects the extent of glycation processes in biological samples, was measured by a standard amino acid ion exchange chromatography followed by reverse phase high pressure liquid chromatography. Infants of diabetic mothers had significantly higher cord glucitollysine levels than infants of control mothers (14.3+4.6 vs. 5.5+2.1 ng/mg dry tissue; M+SD, p <0.001). Moreover, five infants of diabetic mothers with congenital anomalies had strikingly high glucitollysine levels, higher than the mean +4 SD of the controls. We conclude, that non-enzymatic glycation of fetal tissue does occur as a result of an in utero exposure to cumulative glycemia. Major congenital anomalies in diabetic pregnancies are associated with a greater extent of non-enzymatic glycation of umbilical cord tissue.     

Congenital Malformations: A Review of 672 Autopsies in Ibadan, Nigeria

The postmortem findings in 672 Nigerian children with lethal congenital malformations are reviewed. Eighty-six percent of the patients were less than 1 year of age and the male-to-female sex ratio was 1.3:1. The alimentary tract was the most common anatomic site involved (30%), intestinal and biliary atresia being the two lesions most frequently identified in this location. Twenty-six percent of the children had cardiovascular malformations, of which ventricular septal defect, patent ductus arteriosus, and tetralogy of Fallot were most important. There was an accentuated male predominance among cases with urogenital malformations due to the high frequency of posterior urethral valve. Hydrocephalus, spina bifida, and anencephaly were the most common lesions observed in the craniospinal axis. One-fifth of the children had complex malformations of multiple organ systems, 20% of which were associated with chromosomal anomalies, rubella, and other malformation syndromes.     

Population Surveillance of Congenital Malformations Possibilities and Limitations

ABSTRACT. The paper discusses the possibility of detecting newly introduced teratogenic agents by a population surveillance of congenital malformations. In practice, only outbreaks of previously rare malformations or combinations of malformations can be detected by such systems. The most important aspect of malformation surveillance is therefore a detailed reporting of malformations whereas statistical techniques play a minor role. For ongoing surveillance, a high ascertainment level is less important than speed and amount of detail. For studies of longtime changes in malformation rates, ascertainment must be as complete as possible. Such changes have been identified repeatedly, but are usually explained by changes in diagnosis, ascertainment or population characteristics.     

Magnesium and Zinc in Diabetic Pregnancy

ABSTRACT. The concentrations of zinc and magnesium in serum were investigated in 23 non-pregnant and 14 pregnant women with insulin-dependent diabetes (IDDM) and 20 with gestational diabetes, and in cord blood from newborns of the latter two groups. These groups were compared with healthy women, non-pregnant as well as parturient, and newborns of the latter. In the non-pregnant state the mean serum concentrations of zinc and magnesium were lower in IDDM patients than in healthy control women. Although a decrease in S-Zn and S-Mg was obsenwl during pregnancy in both IDDM and control subjects, the difference between carefully insulin-treated IDDM patients and controls was no longer apparent at term of pregnancy as regards S-Zn, whereas S-Mg was lower at term both in IDDM patients and in insulin-treated women with gestational diabetes. Besides the probable importance of a nearly normalized glucose metabolism in IDDM patients during pregnancy, it is postulated that the altered pattern of plasma proteins in diabetes and pregnancy, and possibly also exogenous insulin may influence the serum concentrations of zinc and magnesium seen at the end of pregnancy.     

Zinc, Pregnancy and Parturition

ABSTRACT. The role of zinc in the nutrition of pregnant women and its relations to prenatal growth and parturition are reviewed. Zinc deficiency (ZD) affects fetal growth and development both in experimental animals and in man. The teratogenicity of zinc deficiency was widely demonstrated in animals and is also evident in humans. Alcohol intoxication potentiates the effects of ZD in animals. Plasma zinc levels decrease during pregnancy and apparently an adequate and continuous intake of zinc is required for a normal embryonic development. The zinc content of amniotic fluid seems to be related with fetal growth but its value as an indicator of embryonic development is controversial. Zinc deficiency also affects adversely parturition. Mild zinc deficiency may affect a large number of pregnant women, being potentially harmful to the mother and the fetus. This situation requires the screening of high-risk groups, the definition of adequate dietary intakes for each population, and the supplementation with zinc when deficits are detected.     

Congenital Malformations in Newborns from Diabetic Mothers*

It has been well known that there is a high incidence of congenital malformations in newborns from diabetic mothers when the mothers' diabetes control before and during pregnancy is poor. We treated 438 pregnant diabetics who bore 443 children between February 1964 and June 1992. Among these children, there were 51 cases (11.5%) with congenital malformations, 21 cases with major anomalies (4.7%) and 30 cases with minor anomalies (6.8%). The type of malformations are not related to special organs; heart malformations and cleft lips are relatively frequent compared to other types of malformations. The mechanism of the congenital malformations in newborns from diabetic mothers remains unclear. However, clinically and experimentally it has been found to be due to fuel-mediated teratogenesis. Since October 1978, HbAi has been used as an index of diabetic control and the relationship between congenital malformations and the mother's diabetes control has been observed. 1) There is no difference in the incidence of malformations in children from IDDM and NIDDM mothers. However, there are more severe malformations in the children from IDDM mothers compared to those from NIDDM mothers. 2) Mothers who bore children with major malformations had all made their first visit to our hospital after pregnancy. HbAi in the IDDM mothers who had children with malformations at the first visit was 11%. 3) In the NIDDM mothers, even if HbAi levels are near normal, children with major malformations were born and there was little relationship between congenital malformations and the mothers' diabetes control. These data suggest that there are two kinds of congenital malformations in children from diabetic mothers, fuel-mediated teratogenesis, and malformations as seen in children from non-diabetic mothers.     

Obstetric Care in Diabetic Pregnancy

ABSTRACT. In diabetic pregnancy near-normalization of maternal blood glucose levels improves the perinatal outcome. Strict metabolic control can be achieved by self-monitoring of blood glucose in ambulant praxis. The obstetric supervision may now therefore be organized on an out-patient basis aiming at early recognition of pregnancy complications such as preeclampsia and deviation in fetal growth. For uncomplicated and well-controlled diabetes without vascular complications the obstetric care should be individualized and routine programmes for obstetric surveillance, such as fetal heart rate monitoring and determination of fetal maturity, are usually not necessary. Special attention should, however, be paid to patients with poor metabolic control or vascular complications, particularly in the presence of disturbances of intra-uterine growth.     

Induction of Congenital Malformations in Mice by Paternal Methylnitrosourea Treatment

ABSTRACT A single dose of methylnitrosourea (MNU, 25–100 mg/kg) was injected intraperitoneally into ICR strain male mice. The males were mated to untreated females of the same strain on days 1–21 and 64–80 after the treatment. On day 18 of pregnancy, the fetuses were examined for external and skeletal abnormalities. MNU treatment of paternal germ cells caused significant increases in the incidence of abnormal fetuses over the control level. The induction rate per live fetus per unit dose in mg/kg by treating spermatogonial stem cells was estimated to be 3.0 × 10⁻⁴, which is quite similar to the rate previously estimated for the same endpoint at the same germ cell stage with the fractionated doses of MNU (daily doses at 5–25 mg/kg for 5 days). Cleft palate and dwarfism were the most frequent external abnormalities in the MNU-treated and the control series. Malformed ribs was the most frequent skeletal abnormality in the treated series. It was concluded that congenital malformations induced after treating male mice with a single dose of MNU were quantitatively and qualitatively similar to those induced after treating male mice with the fractionated doses of MNU.     

The Incidence of Congenital Malformations in Various Socioeconomic Groups in Sweden

The incidence of congenital malformations reported to the Register of Births during 1976–77 in various socioeconomic groups were studied combining the informations from the birth register with that from the 1975 census (including occupation of the mother, income of the family, type of family and housing standard). The total population of 190 024 infants were divided into three groups; 6915 infants (3.6 %) were assigned to the most privileged group (group I) and 26430 (13.9 %) to the less privileged group (group III). The total incidence of 5.01 % of any malformation did not differ significantly between the groups. Neither was any variation found for specific malformation types, such as neural tube defects, cleft palate or morbus Down     

Follow-up validation study of the Victorian Congenital Malformations Register

Objective: To determine whether there has been an improvement in ascertainment of malformations in the Victorian Congenital Malformations Register (VCMR).
Methodology The medical records of 500 children under 4 years of age admitted consecutively to two paediatric teaching hospitals in Victoria in 1992 were viewed to determine whether these cases had been notified to the Register.
Results Over three-quarters of the defects recorded had been notified to VCMR. There was 100% ascertainment of chromosomal anomalies and a high proportion of major structural malformations were notified.
Conclusion This study repeats the validation study completed in 1986 and shows marked improvement in ascertainment of malformations in the VCMR by 1992.     

DEALING WITH SUSPICIONS OF MALFORMATION FREQUENCY INCREASE: Experience with the Swedish Register of Congenital Malformations

Abstract. Källén, B. and Winberg, J. (Department of Embryology, University of Lund and Department of Paediatrics at the Karolinska Hospital, Karolinska Institute, Stockholm). Dealing with suspicions of malformation frequency increase, Experiences with the Swedish Register of Congenital Malformations. Strategies in dealing with data obtained from malformation monitoring based on experiences with the Swedish monitoring systems, operating since 1965 (Register of Congenital Malformations) and 1973 (Medical Birth Register) are discussed. The importance of checking data that have sounded an alarm is stressed. Experience has shown that false alarms due to artefacts, such as changed diagnostic routines, changed reporting or registration of malformations, or random fluctuations, comprise most suspected changes in incidence. If a true increase in malformation frequency or a local cluster is observed, a hint of possible aetiological factors can be obtained from studies of maternal age distribution, seasonal variation, geographical distribution, etc. The last step of the analysis consists of a case-control or a cohort study, aimed at revealing a specific teratogen. The importance of locating limited research resources to well-defined problems using high quality data is stressed.     

Cardiac Malformations in Fetuses of Gestational and Pre Gestational Diabetic Mothers

Objective

In this study we aimed to determine the prevalence of cardiac malformations in fetuses of Iranian diabetic mothers with pre-gestational and gestational diabetes mellitus (GDM) and to find the patterns of different cardiac malformations.

Methods

One-hundred and seventy diabetic pregnant women (68 preGDM and 102 GDM) (mean age: 32.17±4.8 years) and 85 healthy controls (mean age: 31.35±4.55 years) were recruited from September 2008 to July 2012. Fetal echocardiography was performed to assess cardiac malformation. In order to study major factors that may affect the results, a complete history was obtained.

Findings

Fetal echocardiography was performed at mean gestational age of 24.7±5.4 and 20.27±3.9 weeks in diabetic patients and control group, respectively. Fifteen (8.8%) fetuses of diabetic mothers were detected to have cardiac malformations compared with 1 (1.17%) fetus in control group (OR: 8.13, 95%CI: 1.1-62.61, P-value=0.02). Hypertrophic cardiomyopathy noted as the most common cardiac malformation occurred in 6 out of 15 (40%) fetuses, and was found significantly more common in pre-GDM compared to GDM group (7.4% vs 1%, P-value =0.04). Despite the higher incidence of cardiac malformation in pre-GDM compared to GDM group, the difference was not significant. Further, no significant association was observed between the variables including; parity, diabetic regimen, parents’ consanguinity, maternal history of hypertension or hypothyroidism and occurring cardiac malformations (P-value>0.05).

Conclusion

In this study we detected cardiac malformations in 8.8% of our diabetic referrals. The result of the present study shows that screening diabetic mothers for fetal cardiac malformations could be beneficial.     

Abdominal Congenital Malformations in Low- and Middle-Income Countries: An Update on Management

Surgical disease has gained increased attention in recent years as contributing to the substantial global burden of disease. Congenital anomalies and surgically correctable ailments of newborns, such as those affecting the chest and abdomen, often require initial intervention with potential for long-term, disease-free survival. The true prevalence of these conditions, however, and the available resources for their management in low- and middle-income countries are unclear. This chapter provides an overview of congenital abdominal anomalies within the context of low- and middle-income countries, and a practical guide to recognition and initial management of those who present for care.     

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.     

Evaluating the accuracy of Malformations Surveillance Program in detecting virilization due to congenital adrenal hyperplasia

Malformations surveillance programs of newborn infants have been developed as a method for identifying serious and relatively common birth defects. The virilization of newborn infants with the classic 21-hydroxylase form of congenital adrenal hyperplasia must be identified early if the associated metabolic crisis in the perinatal period is to be prevented. We compared the detection of virilization associated with 21-hydroxylase congenital adrenal hyperplasia in infants by three methods: an 'active' malformations surveillance of medical records at a large urban hospital; routine medical care by examining physicians; and newborn biochemical screening of blood samples. The experience at a large maternity center in Boston, since 1972, showed that pediatricians often recognized affected females (6/6), but not males (0/2); the state newborn screening program, begun in 1990, identified correctly all affected males and females. The Active Malformations Surveillance Program was the least effective screening method, identifying four of six affected females and neither of the affected males. The low rate of detecting affected females by the Surveillance Program was attributed to a failure to sensitize the research assistants to the importance of physicians' notations regarding the signs and symptoms of virilization. The failure of examining physicians, and thereby, the malformations surveillance program, to detect virilized newborn males was due to the lack of consistent associated physical features. These comparisons between these three methods of detection can be used to design and improve malformations surveillance programs.     

Congenital Humero-radio-ulnar Synostosis with Constriction Ring and Flexion Contracture of the Fingers: A Case Report

ABSTRACT Congenital humero-radio-ulnar synostosis (HRUS) is a rare malformation. Some cases are hereditary in origin and some are sporadic. We report on a sporadic case of HRUS.
A patient with HRUS is described who had constriction ring on the left upper limb and flexion contracture of the wrist joint and fingers. There was no range of motion nor crease at the elbow joint. Hypoesthesia was noted at the distal part of the ring of the upperarm as she did not respond to pin-prick. But circulatory failure like cyanosis or congestion was not seen on the extremity. No operation was performed to release the constrictive ring because it was not so deep. Only splint was applied to correct flexion contracture of the thumb, middle finger and ring finger. Three months later, examination of the thumb and fingers showed full extention. The sense to pain by pin-prick has been improved as the ring on the upperarm shallowed. A minor ischemic change may have been caused by the ring and followed by the contracture and the sensory disturbance. Synostosis also may have been related with the ring.     

The tip of the iceberg: A validation study of the Victorian Congenital Malformations/Birth Defects Register

Abstract Among 1500 children under 4 years of age admitted consecutively to two paediatric teaching hospitals in Victoria in 1985 the prevalence of birth defects was 20%. Fewer than half of these defects had been notified to the Victorian Congenital Malformations Register. Only chromosomal anomalies and, to a lesser extent, major structural malformations present at birth were adequately ascertained. The implications for birth defects monitoring and for service planning are discussed.