Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study

Although the excess risk for birth defects among children of mothers with diabetes mellitus is well documented, there are few data concerning the risk for specific malformations. In the Atlanta Birth Defects Case-Control Study, those risks for malformations were evaluated. The population-based study included 4929 live and stillborn babies with major malformations ascertained by the Metropolitan Atlanta Congenital Defects Program in the first year of life born to residents of Metropolitan Atlanta between 1968 and 1980. The study also included 3029 nonmalformed live babies who were frequency-matched to case babies by race, period of birth, and hospital of birth. The relative risk for major malformations among infants of mothers with insulin-dependent diabetes mellitus (n = 28) was 7.9 (95% confidence interval [CI]1.9, 33.5) compared with infants of nondiabetic mothers. The relative risks for major central nervous system and cardiovascular system defects were 15.5 (95% CI = 3.3, 73.8) and 18.0 (95% CI = 3.9, 82.5), respectively. The absolute risks for major, central nervous system, and cardiovascular system malformations among infants of diabetic mothers were 18.4, 5.3, and 8.5 per 100 live births, respectively. Infants of mothers with gestational diabetes mellitus who required insulin during the third trimester of pregnancy were 20.6 (95% CI = 2.5, 168.5) times more likely to have major cardiovascular system defects than infants of nondiabetic mothers. The absolute risk for infants of this group of diabetic mothers was 9.7%. No statistically significant differences were found among infants of mothers with gestational diabetes mellitus who did not require insulin during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monitoring of congenital cardiac defects

Summary An effort was made to identify all infants born with a congenital cardiac defect in 1981 in Sweden by using four different registries: the Swedish Registry of Congenital Malformations, the Medical Birth Registry, the Registry of Death Certificates, and a specially designed Child Cardiology Registry. All infants diagnosed before the age of one year at one of the five child cardiology clinics in Sweden were reported to the latter registry. This registry, together with the Congenital Malformation Registry, can be used for surveillance as they together cover 85%–90% of all severe cases identified. The data quality in the Medical Birth Registry is too low to permit meaningful surveillance. A total of 853 infants with a diagnosis of a congenital cardiac defect were identified. This represents 9 per 1000 newborns. Many of the cases were dubious, but the diagnosis was stated as probable in 708 (7.6 per 1000); 146 infants died. Cardiac diagnoses were stored in the Child Cardiology Registry and in the Registry of Congenital Malformations as ISC codes. A Monitor Code is described that can be used for grouping and monitoring of diagnoses. Using these codes, data in the Child Cardiology Registry for 1981–1983 were analyzed and epidemiologic information on maternal age and parity, sex rate, and birth weight distribution is given.     

Association between maternal pre-existing or gestational diabetes and health problems in children

There is general consensus that children of women with pre-existing diabetes mellitus (PDM) have an increased risk of malformations and neurodevelopmental problems. Whether this is also true for children of women with gestational diabetes mellitus (GDM) is a matter of debate. This study investigated inpatient hospital care up to 10 y of age of children born to GDM and PDM women as a rough estimate of child morbidity. Hospital care of children born to 82 684 GDM women, 3874 PDM women and 1213957 controls was compared by linking the Swedish Medical Birth Registry with the Hospital Discharge Registry. Similar comparisons were performed in a local well-controlled group of 326 children born to GDM women in the Lund area. Children of PDM women and to a lesser degree children of GDM women had a statistically significant increase in hospitalizations, evident at least up to 10 y of age. Significantly increased risks of hospitalization were found for neurological/developmental disorders [odds ratio (OR) 2.30 and 1.36 for PDM and GDM, respectively)], malformations (OR 2.05 and 1.23), infections (OR 1.56 and 1.20) and accidents (OR 1.32 and 1.14). Conclusion: The high hospitalization rates of these children indicate an increased morbidity, including neurodevelopmental disorders.     

Population-based case-control study of oral ketoconazole treatment for birth outcomes

The objective of the study presented here was to check the effect of oral ketoconazole treatment on fetal development. Ketoconazole has been given a teratogenic classification of C by the US Food and Drug Administration, but human controlled epidemiological studies of the treatment's effects have not been reported. The occurrence of ketoconazole use in the second to third months of gestation was compared between cases with congenital abnormalities and their matched controls in the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Birth weight and gestational age were evaluated in control newborn infants born to mothers with or without ketoconazole treatment. The case group comprised 22,843 cases with congenital abnormalities, while the control group contained 38,151 newborn infants without any defects. Six infants (0.03%) and 12 controls (0.03%) had mothers who had received oral ketoconazole treatment (prevalence odds ratio: with 95% confidence interval: 0.8, 0.3-2.2). No group of infants with congenital abnormalities had mothers with a higher incidence of use of the drug. The mean gestational age was somewhat longer while birth weight was somewhat larger in controls with ketoconazole treated mothers. Our study failed to demonstrate a higher rate of congenital abnormalities in infants with mothers who had received oral ketoconazole treatment during pregnancy.     

Noncardiac Malformations at Major Congenital Heart Defects

Using the Swedish Cardiology Registry and the Registry of Congenital Malformations, and after excluding infants with a known chromosomal anomaly, data on 397 infants (15%) born during the period 1981–1990 with a major cardiac defect and at least one noncardiac malformation were analyzed. No clear-cut association appeared between specific heart defects and major groups of noncardiac malformations except for a possible relation between spleen anomalies and endocardial cushion defects. Specific associations also appeared between common truncus and limb reduction defects and between transposition of the great vessels and situs inversus. However, the small numbers of infants in the latter groups and the large number of tested hypotheses make it difficult to exclude chance associations.     

Infants of diabetic mothers are at increased risk for the oculo-auriculo-vertebral sequence: A case-based and case-control approach

OBJECTIVES: To determine if infants of diabetic mothers (IDM) are at increased risk for dysplastic ears and the oculoauriculo-vertebral spectrum (OAVS). STUDY DESIGN: Cases of IDM with dysplastic external ears seen at Cedars-Sinai Medical Center were combined with case series in medical literature describing similar patients. Data from a large congenital birth defects registry in Spain were analyzed, and odds ratios (OR) for infants born to either a gestational or preconceptionally diabetic mother to have one of the studied malformations were calculated with 95% confidence intervals. RESULTS: Among the 30 patients in the case series, 50.0% (15) had hemifacial microsomia; 46.7% (14) had hearing loss; 33.3% (10) had facial nerve palsy; 33.3% (10) had vertebral anomalies; 36.7% (11) had cardiovascular defects, of which 45% (5) were conotruncal defects; 26.7% (8) had renal anomalies; 13.3% (4) had limb defects (all radial ray hypoplasia); 10% (3) had DiGeorge sequence; 6.7% (2) had laterality defects; and 6.7% (2) had imperforate anus. Within the cases from the birth defects registry, the odds ratio for OAVS in infants of mothers with gestational diabetes mellitus was 2.28 (95% CI, 1.03-4.82, P =.03), and the OR for ear anomalies in these infants was 1.21 (95% CI, 0.94-1.56, P =.13). When infants of mothers with preconceptionally diagnosed type 1 or 2 diabetes were considered, the OR for OAVS was 1.50 (95% CI, 0.08-9.99, P =.49), and the OR for dysplastic ears was 0.94 (95% CI, 0.48-1.81, P =.85). CONCLUSIONS: Our data indicate that OAVS occurs with a higher incidence in IDM than in the general population. Associated problems include hearing loss, athymia, and cardiac, renal, and limb malformations. Therefore, we recommend that an IDM with features consistent with OAVS undergo a workup including hearing evaluation, skeletal survey, echocardiogram, renal ultrasonogram, and immunodeficiency workup if clinically indicated. Furthermore, noting that most of these defects occur in structures of neural crest origin, we hypothesize that poorly controlled maternal diabetes interferes with cephalic neural crest cell migration.     

Sudden infant death syndrome and post perinatal mortality in Norwegian birth cohorts 1967-1980

The well established effects of maternal age and birth order in sudden infant death syndrome (SIDS) formed the basis for a comparison with other categories of post perinatal death in an attempt to shed some light on the etiologic roles played by ante and postnatal factors. A total of 826,162 children, born 1967 through 1980 and recorded at the Medical Birth Registry of Norway was at risk to die during the post perinatal period (ages 7 through 364 days). Out of the 3,582 infants who died, 1,062 were considered SIDS. Strong effects of maternal age (negative) and birth order (positive) were found in the SIDS group, but not to the same extent in the non-SIDS group or the group of congenital malformations. Likewise, the excess risk in children of unmarried mothers was higher in the SIDS group. The suggested effects of postnatal factors in the causation of SIDS may seem promising from a preventive point of view. The strength of the effects of maternal age and birth order necessitate adjustment for these variables in future epidemiological studies of SIDS.     

Gestational diabetes and offspring body disproportion

Aim:  It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants.
Methods:  Birth characteristics of 884 267 infants of non-diabetic mothers and 7817 of mothers with GDM were analysed. LGA was defined as birth weight or birth length >2 standard deviation scores for gestational age. Multiple logistic regression analysis was performed.
Results:  The odds ratio (OR) for a woman with GDM to give birth to an LGA infant that was heavy alone was four times increased (OR: 3.71, 95% CI: 3.41–4.04). Furthermore, in the population of mothers giving birth to LGA infants, the proportion heavy alone was 68% in the group of women with GDM compared with 64.4% in the group of non-diabetic women. The risks were independent of gender of the foetus.
Conclusion:  Women with GDM have an almost four times higher risk of delivering an LGA infant that is heavy alone. The noted disproportion between weight and length in infants of such mothers may have an impact on the risk of later obesity.     

Sudden Infant Death Syndrome and Post Perinatal Mortality in Norwegian Birth Cohorts 1967-1980

ABSTRACT. The well established effects of maternal age and birth order in sudden infant death syndrome (SIDS) formed the basis for a comparison with other categories of post perinatal death in an attempt to shed some light on the etiologic roles played by ante and postnatal factors. A total of 826162 children, born 1967 through 1980 and recorded at the Medical Birth Registry of Norway was at risk to die during the post perinatal period (ages 7 through 364 days). Out of the 3582 infants who died, 1062 were considered SIDS. Strong effects of maternal age (negative) and birth order (positive) were found in the SIDS group, but not to the same extent in the non-SIDS group or the group of congenital malformations. Likewise, the excess risk in children of unmarried mothers was higher in the SIDS group. The suggested effects of postnatal factors in the causation of SIDS may seem promising from a preventive point of view. The strength of the effects of maternal age and birth order necessitate adjustment for these variables in future epidemiological studies of SIDS.     

Maternal smoking during pregnancy and infant head circumference at birth

Using the Swedish Medical Birth Registry, information on 1,362,169 infants born during 1983-1996 was analyzed in order to investigate the relation between maternal smoking during pregnancy and infant head circumference at birth. Infants of smoking mothers were at an increased risk to have head circumference <32 cm, and the adjusted odds ratios (OR) with 95% confidence intervals (CI) for any smoking, smoking <10 cigarettes per day, and smoking >/=10 cigarettes per day were: 1.65 (1.62-1.68), 1.52 (1.48-1.56), and 1.86 (1.81-1.92), respectively. A highly significant association between small head circumference for gestational age and maternal smoking was also found (ORs (with 95% CI) were for any smoking, <10, and >/=10: 1.58 (1.55-1.61), 1.48 (1.45-1.51), and 1.74 (1.70-1.79), respectively). For both outcomes, the observed dose-response effects were highly significant (P<10(-6)). Even more alarming was the finding that given a certain level of growth retardation, infants of smoking mothers were at an increased risk of small head circumference for gestational age compared to infants of non-smoking mothers (OR (with 95% CI) for any smoking adjusted for 'percentage of expected birth weight': 1.08 (1.06-1.10)). Given the evidence that maternal smoking specifically affects head growth, until contradictory evidence has been found, it seems reasonable to assume that maternal smoking during pregnancy affects brain development negatively.     

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.     

Females born large for gestational age have a doubled risk of giving birth to large for gestational age infants

AIM: To analyse if females born large for gestational age (LGA) have an increased risk to give birth to LGA infants and to study anthropometric characteristics in macrosomic infants of females born LGA. METHODS: The investigation was performed as an intergenerational retrospective study of women born between 1973 and 1983, who delivered their first infant between 1989 and 1999. Birth characteristics of 47,783 females, included in the Swedish Birth Register both as newborns and mothers were analysed. LGA was defined as >2 SD in either birth weight or length for gestational age. The infants were divided into three subgroups: born tall only, born heavy only and born both tall and heavy for gestational age. Multiple logistic and linear regression analyses were performed. RESULTS: Females, born LGA with regard to length or weight, had a two-fold (adjusted OR 1.96, 95% Cl 1.54-2.48) increased risk to give birth to an LGA infant. Females, born LGA concerning weight only, had a 2.6 (adjusted OR 2.63, 95%, 1.85-3.75) fold increased risk of having an LGA offspring heavy only and no elevated risk of giving birth to an offspring that was tall only, compared to females born not LGA. In addition, maternal obesity was associated with a 2.5 (adjusted OR 2.56, 95%, 2.20-2.98) fold increased risk of having an LGA newborn, compared to mothers with normal weight. CONCLUSION: Females, born LGA, have an increased risk to give birth to LGA infants, compared to mothers born not LGA. Maternal overweight increases this risk even further.     

High incidence of Down's syndrome in infants of diabetic mothers

The incidence of Down''s syndrome was studied in 1870 infants of diabetic mothers out of 22 300 neonates born between January 1987 and April 1994 in our institution. All pregnancies were screened for diabetes and all cases of Down''s syndrome were confirmed by chromosome analysis.
Down''s syndrome (all trisomy 21) was diagnosed in 35 infants: seven were born to mothers with gestational diabetes and 28to non-diabetic mothers. The incidence of Down''s syndrome was higher in infants of diabetic mothers (3.75 per 1000 v 1.36 per 1000) (p= 0.02) with a relative risk of 2.75. No significant difference was found in maternal age between both groups (p= 0.67) and the rate of Down''s syndrome was higher in infants of diabetic mothers when compared with infants of non-diabetic mothers of similar age.
Down''s syndrome should be added to the congenital malformations already known to occur more frequently in infants of diabetic mothers.

     

Embryonal risks in gestational diabetes mellitus

Diabetes mellitus is generally associated with a higher incidence of early pregnancy loss and congenital anomalies, though this relationship should be strictly restricted to patients with previously existing diabetes. In gestational diabetes mellitus, which often develops during the third trimester, no such relationship should exist, though the birth of a previous infant with a congenital anomaly is often assumed to be a risk factor for gestational diabetes. OBJECTIVE: The study attempts to analyse the congenital anomaly rate in women with gestational diabetes and compare this to the rates in women known to have normal glucose tolerance. RESULTS: The prevalence of infants/fetuses with congenital anomalies born to women with gestational diabetes amounted to 4.48%, a rate similar to that recorded in women with normal glucose tolerance (4.54%). CONCLUSIONS: The development of gestational diabetes, in contrast to pre-existing diabetes, does not appear to be associated with an increased risk for teratogenesis.     

Congenital malformations in Shimla

Congenital malformations were studied over a period of five years in 10, 100 consecutive births including still births at Indira Gandhi Medical College, Shimla. Out of these, 180 babies had one or the other congenital malformations and the overall incidence was 1.78%. Amongst the 311 still born babies 47 had congenital malformations indicating that the incidence of congenital malformations was much higher in still born babies (15.1%) as compared to the live born babies (1.3%). The malformations involving the central nervous system were the commonest (40%) followed by musculoskeletal system (23.8%) while genitourinary system malformations were the least common and accounted for 3.8% of the cases. Incidence of congenital malformations was the highest in mothers over 35 years of age and gravida four and more. The incidence was 2.8% in both the groups; the incidence of congenital malformation was more in babies weighing < 2500 gms and was 2.6%.     

歪嘴哭面容新生儿的临床特征及随访研究

目的：评估歪嘴哭面容新生儿的临床特征及近期转归,为临床医师更深刻地认识该疾病提供信息。方法：回顾性研究2010年1月至2012年2月间收治的11例歪嘴哭面容患儿的临床特点,随访纠正胎龄44周和3月龄时的体格及神经发育情况。结果：11例歪嘴哭面容患儿中,4例合并同侧耳部发育异常,2例先天性心脏病,1例多指和并指畸形。男性8例,女性3例。8例病变为左侧,3例为右侧。父亲年龄超过35岁者8例,母亲年龄超过30岁者7例;多次妊娠者8例,不良孕产史者4例,母亲妊娠期糖尿病者2例。纠正胎龄44周时1例体格发育指标在同胎龄同性别的P10以下,2例NBNA评分小于35分,2例GMs评估扭动阶段为单调（轻度异常）;生后3月时11例患儿体格发育指标均在P10~P90之间,GMs评估不安运动阶段均正常,但歪嘴哭面容均无改善。结论：歪嘴哭面容患儿易合并其他畸形;患儿预后相对较好,但仍需长期随访,适时给予多学科合作干预。     

Erythrocyte indicators of oxidative stress in gestational diabetes

Foetuses born to mothers with gestational diabetes are at increased risk of developing respiratory distress, foetal macrosomia, foetal anomalies and platelet hyperaggregability. High blood glucose level induces oxidative stress and decreases antioxidant defences. The present study discusses the possibility of lipid peroxidation and protein oxidation in both maternal and foetal erythrocytes as an indicator of oxygen radical activity. The level of lipid peroxidation and protein oxidation in erythrocytes was estimated in 20 mothers with gestational diabetes and their newborns. The maternal age varied between 19 and 42 y and foetal age ranged between 34 and 39 weeks. The proteolytic activities in the erythrocyte lysates obtained from mothers with gestational diabetes and their newborns were significantly greater [(mean ± SD) 24.41 ± 9.05 and 16.70 ± 3.36μM of amino groups/g haemoglobin, n = 20, respectively] than those from control group (10.18 ± 4.84 and 14.64 ± 6.21 μM amino groups/g haemoglobin, n = 15, respectively; p < 0:05 in both cases). Similarly erythrocyte malondialdehyde levels were significantly elevated in babies born to mothers with gestational diabetes (10.11 ±2.21 nM/g haemoglobin) when compared to controls (6.8 ± 3.75 nM/g haemoglobin) (p < 0:05). In the erythrocytes of mothers with gestational diabetes, malondialdehyde levels correlated significantly with glycated haemoglobin levels (p < 0:01). The results of this study indicate that the oxidative stress induced by gestational diabetes manifests as increased lipid peroxidation and protein oxidative damage in the erythrocytes of both mothers with gestational diabetes and their newborn infants.