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.     

Experience with anorectal malformations in Ile-Ife, Nigeria

The study was carried out to determine the characteristics and outcome of management of anorectal malformations (ARM) in Nigerian children at the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC) in Ile-Ife, Nigeria, between January 1986 and December 2002. Eighty-six children with ARM were studied, 48 males and 38 females. Only 12 (13.9%) presented to the hospital within 24 h of birth. Twenty-four (27.9%) patients had one or more associated congenital anomalies, with oesophageal atresia with tracheo-oesophageal fistula being the most common associated malformation. A low variety was identified in 26 (30.2%) cases, while 60 (69.8%) had intermediate or high lesions. Twenty-two patients with the low type of anomaly were offered primary anoplasty in the neonatal period, whereas 59 patients with intermediate or high malformations were offered a preliminary colostomy. A definitive pull-through procedure was ultimately performed in 27 of these 59 cases. Twenty-six patients (30.2%) died. Infection and severe associated malformations were responsible for most (65%) of the deaths. Early results of definitive surgery among survivors were generally good after a mean follow-up period of 13 months. Late presentation, inadequate facilities for neonatal intensive care, and paucity of specialist supportive personnel appear to have negatively influenced the outcome of treatment in our environment. Increasing awareness and availability of medical facilities and specialists are needed.     

Belated diagnosis of congenital anomalies

Over a period of 4 years, 84 (9.63%) cases of congenital anomalies in two hospitals in Kumasi, Ghana, were belatedly diagnosed beyond the neonatal period or when complications threatened the life of the patient. The factors leading to the late diagnosis were: (1) the nature and site of the anomaly; (2) beliefs, customs, and enlightenment of the society; and (3) inadequate medical facilities and expertise. The late diagnosis invariably culminated in high morbidity and mortality, problems of management, and social problems. Education of the general public, especially parents, on congenital anomalies as well as improvement of medical and diagnostic facilities are therefore suggested, if not demanded.     

Cryptorchidism in boys with congenital abdominal wall defects

Cryptorchidism (CPT) has been suggested to be common in boys with congenital abdominal wall defects (CAWD). It has been hypothesized that the low intra-abdominal pressure in both omphalocele (OMP) and gastroschisis (GS) and brain malformations in patients with OMP contribute to the high incidence of CPT. To determine the incidence of CPT in boys with OMP and GS and to assess the relationship of CPT to the size of the AWD, prematurity, and concomitant anomalies, the hospital records and autopsy reports of 113 boys with CAWD (OMP n = 75; GS n = 38) were reviewed. Twelve (16.0%) boys with OMP had undescended testes; 5 (41.0%) of those had bilateral and 4 (23.5%) intra-abdominal undescended testes. The occurrence of CPT in OMP patients did not correlate with the size of the AWD, birth weight, or gestational age. However, congenital cardiac anomalies and cleft lip and palate were significantly more common (P < 0.05) among those with CPT. Two (5.0%) boys with GS, both of whom were born prematurely, had inilateral CPT. In patients with OMP, the incidence of CPT was significantly higher than that of healthy children. There was a correlation between CPT and congenital midline defects such as cardiac anomalies and cleft lip and palate. In patients with GS, the incidence of CPT only slightly exceeded that of normal children and may have been related to prematurity. Accepted: 6 January 1997     

Congenital Malformations and Deformations in Provincial Hospitals in Indonesia

A study of congenital malformations and deformations in the neonatal period in 14 hospitals consist of 13 provincial government hospitals as teaching hospitals and one private children and maternity hospital is presented. The incidence of anomalies in the range of 6–15 per thousand of total births. The incidence in boys was higher than girls. Based on the ICD-10, among the 2,621 anomalies, the most frequent of malformations and deformations were those of the musculoskeletal system (19.6%), followed by the nervous system (18.8%), the digestive system (18.7%), the circulatory system (12.9%), and the cleft lip and cleft palate (8.2%). Corrective and reconstructive surgery were performed by the Subspecialistic Division of the Surgical Department.     

Epidemiological study of congenital diaphragmatic defects with special reference to aetiology

Congenital diaphragmatic defects (CDD) are easily accessible to ultrasonographic diagnosis. In spite of progress in the management of prenatally detected cases, the mortality rate for CDD remains high. The prognosis depends mainly on the severity of fetal lung hypoplasia but is also linked to the associated malformations. We report on 77 cases of CDD ascertained between 1982 and 1988 from 136 161 consecutive births in the Bouches du Rhône area. The spontaneous perinatal mortality rate was 61% with 28 early post-natal deaths and 14 stillbirths. Eight pregnancies were terminated after prenatal diagnosis. The diaphragmatic defect was associated with other congenital anomalies in 33 cases, more often among stillborn (92.8%) than liveborn infants (23.6%). A chromosomal abnormality was present in 9 cases representing 11.6% of all CDD and in 27.2% of cases with other anomalies. A Mendelian disorder was present in 9 cases (eight Fryns syndrome and one Fraser syndrome). This study underlines the necessity of a systematic work up of prenatally diagnosed cases, including fetal karyotyping and analysis of associated malformations in order to adapt the management of the pregnancy and delivery to the prognosis.     

The Fate of Children with Microdeletion 22q11.2 Syndrome and Congenital Heart Defect: Clinical Course and Cardiac Outcome

Background This study aimed to evaluate the cardiac outcome for children with microdeletion 22q11.2 and congenital heart defect (CHD). Methods A total of 49 consecutive children with 22q11.2 and CHD were retrospectively identified. The CHD consisted of tetralogy of Fallot and variances (n = 22), interrupted aortic arch (n = 10), ventricular septal defect (n = 8), truncus arteriosus (n = 6), and double aortic arch (n = 1). Extracardiac anomalies were present in 46 of 47 children. Results The median follow-up time was 8.5 years (range, 3 months to 23.5 years). Cardiac surgical repair was performed for 35 children, whereas 5 had palliative surgery, and 9 never underwent cardiac surgery. The median age at repair was 7.5 months (range, 2 days to 5 years). The mean hospital stay was 35 days (range, 7–204 days), and the intensive care unit stay was 15 days (range, 3–194 days). Significant postoperative complications occurred for 26 children (74%), and surgery for extracardiac malformations was required for 21 patients (43%). The overall mortality rate was 22% (11/49), with 1-year survival for 86% and 5-year survival for 80% of the patients. A total of 27 cardiac reinterventions were performed for 16 patients (46%) including 15 reoperations and 12 interventional catheterizations. Residual cardiac findings were present in 25 patients (71%) at the end of the follow-up period. Conclusions Children with microdeletion 22q11.2 and CHD are at high risk for mortality and morbidity, as determined by both the severity of the cardiac lesions and the extracardiac anomalies associated with the microdeletion.     

Association of rib anomalies and malignancy in childhood

A relationship exists between tumours and malformations both generally and in particular combinations. This is also valid for minor errors of morphogenesis suggesting that embryonic tumours are an expression of aberrant intra-uterine morphogenesis. We speculated that these minor aberrations might also manifest in other morphological defects, especially in minor anomalies and malformations of the ribs. We reviewed chest roentgenographs of 1000 children with malignancies for rib anomalies and compared them to 200 patients with mainly infectious diseases. We found 242 rib anomalies in 218 children with tumours (21.8%) and 11 (5.5%) in children without malignancy. This difference was statistically highly significant (P<0.001). A high incidence of cervical ribs was found in neuroblastoma (33%), brain tumour (27.4%), leukaemia (26.8%), soft tissue sarcoma (24.5%), Wilms tumour (23.5%) and Ewing sarcoma (17.1%). Only neuroblastoma showed a high incidence of rib bifurcation (4.5%). The increased incidence of these mesenchymal defects in children with malignancies may be another clue for an altered morphogenesis in tumour origin. In neuroblastoma the rib anomaly may be another expression of neurocristopathy as proposed for the association of congenital heart disease and neuroblastoma.     

Agenesis of the internal carotid artery: associated malformations including a high rate of aortic and cardiac malformations

Background

Agenesis of the internal carotid artery (ICA) is a rare congenital anomaly occurring in less than 0.01% of the population, often incidentally discovered in pediatric populations. We recognized a high incidence of additional congenital malformations in children with ICA agenesis.

Objective

Our study reports nine cases of ICA agenesis and co-existent malformations and discusses implications of the association.

Materials and methods

We conducted a retrospective chart review of nine children evaluated at our institution with imaging findings of ICA agenesis.

Results

Seven children (78%) had congenital aortic or cardiac anomalies including coarctation (4), hypoplastic left heart (1), tetralogy of Fallot (1), and muscular ventricular septal defect (VSD) (1). Four children were diagnosed with an inherited disorder: Alagille syndrome (1), PHACE syndrome (1), VACTERL association (1), and methylenetetrahydrofolate reductase (MTHFR) gene variant (1). Additional congenital anomalies are also described.

Conclusion

In the setting of ICA agenesis, we report a robust association with congenital aortic and cardiac anomalies, as well as a broad spectrum of additional anatomical abnormalities that can occur in the setting of known genetic syndromes or as isolated findings. Knowledge of the natural history of ICA agenesis and associated anomalies will guide optimal care for these children.     

Deaths among children less than two years of age receiving palivizumab: an analysis of comorbidities

BACKGROUND: Palivizumab (Synagis) is used for prophylaxis against respiratory syncytial virus infection among children at high risk for respiratory syncytial virus disease. A number of deaths after palivizumab use among children <2 years have been reported to the Food and Drug Administration. We assessed available information, including the extent to which preexisting medical conditions may have put these children at higher than normal risk of death. METHODS: We reviewed reports of deaths to the Food and Drug Administration (June 1998 to December 2001) among children <2 years of age who received palivizumab. RESULTS: There were 133 deaths reported after palivizumab use. Median age at death was 5 months, and 54% of the children were male. At least one congenital anomaly was reported in 85 cases (64%), and 44% of cases had multiple anomalies. Of the 100 cases with reported gestational age at birth, 36% were severely premature (<28 weeks), 48% were moderately premature (28 to 36 weeks) and 16% had normal gestational age. Only 2% of all cases were full term and were born without congenital anomalies; 50% had both conditions, 34% had prematurity alone and 14% had congenital anomalies alone. A cause of death was reported for 88 (66%) cases; most (38%) died from their congenital anomalies or from respiratory infections (23%). CONCLUSIONS: Most children dying after palivizumab treatment were at increased risk of death; many had multiple congenital anomalies and/or premature birth. Patterns of outcomes and the reported medical course did not suggest that palivizumab further elevated the risk of death. Current data do not alter the safety and efficacy assessment that led to the licensure of palivizumab.     

Prevalence of congenital malformations in Cross River and Akwa Ibom states of Nigeria from 1980-2003

A retrospective study was conducted on the prevalence of congenital malformations in Cross River and Akwa Ibom states of Nigeria from 1980-2003. These states lie in the South-South geopolitical zone of Nigeria. The aim of the study was to determine the percentage of occurrence of birth defects and provide reference data for this part of the country. Details of congenital malformations were compiled by reviewing the delivery register of the records departments of maternity sections of University of Calabar Teaching Hospital, St Luke's Hospital Anua and St Mary's Hospital Uruakpan. A total of 127,929 births were recorded, of which 452 cases of malformations were recorded. The anomalies recorded in the skeletal system were the highest with 132 cases (29.2%) detected. Other malformations were found to be associated with the central nervous system with 111 cases (24.6%) detected. Those associated with the urogenital system were found in 83 cases (18.4%). Congenital anomalies of the lip, palate and jaw were found in 56 cases (12.4%), while those of the eye and ear were found in 12 cases (2.7%). Those of the gastrointestinal tract were found in 29 cases (6.4%), while those of the respiratory and cardiovascular systems were found in 28 cases (6.2%) and in one case (0.2%), respectively. Fifteen cases (3.3%) were associated with chromosomal abnormalities, such as Down syndrome. However, these results do not provide a complete incidence of congenital malformations in the two states studies because most anomalies are not recorded in rural health and traditional birth centers.     

Does Down syndrome affect the outcome of congenital duodenal obstruction?

Congenital duodenal obstruction (DO) has a well-known association with Down syndrome (DS) and other congenital malformations. Previously reported series on DO have not examined the influence of DS on associated congenital malformations and postoperative morbidity and mortality. We report on a retrospective study of all children born with DO over an 11-year period to investigate this. A total of 79 patients with DO were studied: group 1 consisted of 51 (64.6%) children without DS, and group 2 consisted of 28 (35.4%) children with DS. There was no significant difference in mean gestational age and birth weight between groups 1 and 2. A coexisting congenital malformation was found in 68% of patients. Gastrointestinal malformations were the most common in group 1 (71.1%), and cardiac malformations were the most common in group 2 (81.5%). The mean time to reach full intragastric feeds was 12 days, with no significant difference between the two groups (p=0.383). Seven (8.9%) patients developed a postoperative complication, with no significant difference between both groups (p=0.853). A total of 11 patients died: six (12%) in group 1 and five (28%) in group 2, with no significant difference between the groups (p=0.454). DS does not influence the morbidity and mortality of DO but does carry a higher incidence of congenital cardiac abnormalities. Delayed mortality was a result of coexisting congenital cardiac and respiratory disease.     

One hundred three consecutive patients with anorectal malformations and their associated anomalies

OBJECTIVE: A long-term retrospective analysis of 103 infants with anorectal malformations (ARMs) was conducted to describe any associated congenital anomalies and surgical classifications. DESIGN: Retrospective medical record review. SETTING: This case series was conducted on all infants with ARMs born at, or referred to, any of 3 major medical centers in Wichita, Kan, for close to a 22-year period. PATIENTS: The 103 infants in this study represent a consecutive sample of patients with ARMs. Patients were separated into 2 groups: isolated ARMs without associated anomalies (n = 30), and ARMs with associated anomalies (n = 73). The male-female ratio was 2:1. MAIN OUTCOME MEASURES: Patients with associated anomalies were further classified into groups of ARMs with minor anomalies; major anomalies; chromosomal abnormalities; and malformation syndromes, associations, or sequences. Only anomalies that occurred more than once were reported. Malformations were also classified according to major organ systems. RESULTS: The incidence of ARMs in our study was approximately 1 in 2500 live births. Additional anomalies were found in 71% of infants with ARMs. Associated anomalies by major organ system included genitourinary anomalies (49%), musculoskeletal anomalies (43%), craniofacial anomalies (34%), cardiovascular anomalies (27%), gastrointestinal anomalies (18%), respiratory anomalies (13%), and central nervous system anomalies (12%). The most common chromosomal abnormalities were trisomies (8%), and ARMs were associated with VATER complex (vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, and radial and renal anomalies) in 11 cases (11%) and VACTERL (vertebral, anal, cardiac, tracheal, esophageal, renal, and limb anomalies) in 4 cases (4%). CONCLUSIONS: Patients with ARMs have a high incidence of associated congenital anomalies. Evaluation of the most commonly affected organ systems in these infants is essential because it is these associated anomalies that account for most of the morbidity and mortality that is associated with this condition.     

Mortality from congenital malformations in England and Wales: variations by mother's country of birth.

Stillbirth and infant mortality from congenital malformations in England and Wales during 1981-5 was investigated according to the mother''s country of birth. Significant differences remained after standardising for maternal age and social class. The highest overall mortality was in infants of mothers born in Pakistan (standardised mortality ratio 237), followed by infants of mothers born in India (standardised mortality ratio 134), East Africa (standardised mortality ratio 126), and Bangladesh (standardised mortality ratio 118). Caribbean and West African mothers showed an overall deficit. Mortality was inversely related to social class in all groups except the Afro-Caribbean. Infants of mothers born in Pakistan had the highest mortality in every social class except I, and for most anomalies investigated. Their ratios were particularly high for limb and musculoskeletal anomalies (standardised mortality ratio 362), genitourinary anomalies (standardised mortality ratio 268), and central nervous system anomalies (standardised mortality ratio 239). Our findings highlight the need for further research to identify the causes underlying these differences.     

High mortality due to congenital malformations in children aged &lt; 1 year in French Guiana

Background

In French Guiana, pregnant women may be exposed to infectious, environmental, and social risks leading to congenital malformation. The objective of the study was to study mortality rates from congenital malformations among infants <?1?year and to compare them with those in mainland France.

Methods

We used the CEPI DC (INSERM) database, which compiles annual data from death certificates in all French territories using the International Classification of Diseases. Annual deaths for French Guiana and mainland France between 2005 and 2015 were compiled. The age category studied was children less than 1?year and deaths from congenital malformations, deformations and chromosomal abnormalities were compiled. Crude risk ratios and 95% confidence intervals were calculated to quantify the excess risk of disease in French Guiana.

Results

In French Guiana between 2005 and 2015 there were 666 deaths of children aged <?1?year, among which, 132 (19.8%) were due to congenital malformations and chromosomal anomalies. Overall the risk ratio of death from congenital malformations and chromosomal anomalies between French Guiana and mainland France was 2.7 (1.5–4.7), P?<?0.001 for neurological congenital malformations it was 4.8 (1.2–19.7), P?=?0.01 and for congenital malformations of the circulatory system it was 3.3 (1.5–6.9), P?=?0.001.

Conclusions

The incidence of death from congenital malformations or chromosomal anomalies in French Guiana was significantly higher than in mainland France. Explanations for this may be infections, genetic causes, nutritional causes, and toxic causes that are prevalent. There is a need to identify factors that predispose children born in French Guiana to having a higher risk of congenital malformations and chromosomal anomalies.

     

Congenital hydrocephalus – prevalence,prenatal diagnosis and outcome of pregnancy in four European regions

ObjectiveTo describe prevalence, prenatal diagnosis and outcome for fetuses and infants with congenital hydrocephalus.MethodsData were taken from four European registries of congenital malformations (EUROCAT). The registries included are based on multiple sources of information and include information about livebirths, fetal deaths with GA ≥ 20 weeks and terminations of pregnancy for fetal anomaly (TOPFA). All cases from the four registries diagnosed with congenital hydrocephalus and born in the period 1996–2003 were included in the study. Cases with hydrocephalus associated with neural tube defects were not included in the study.ResultsEighty-seven cases with congenital hydrocephalus were identified during the study period giving an overall prevalence of 4.65 per 10,000 births. There were 41 livebirths (47%), four fetal deaths (5%) and 42 TOPFA (48%). Nine percent of all cases were from a multiple pregnancy. Additional non-cerebral major malformations were diagnosed in 38 cases (44%) and karyotype anomalies in eight cases (9%). Median GA at TOPFA was 21 weeks. Among livebirths 61% were diagnosed prenatally at a median GA of 31 weeks (range 17–40 weeks) and median GA at birth was 37 weeks. Fourteen liveborn infants (34%) died within the first year of life with the majority of deaths during the first week after birth.ConclusionCongenital hydrocephalus is a severe congenital malformation often associated with other congenital anomalies. CH is often diagnosed prenatally, although sometimes late in pregnancy. A high proportion of affected pregnancies result in termination for severe fetal anomaly and there is a high mortality in livebirths.     

Congenital malformations at birth among liveborn infants in Afghanistan,a prospective study

In a prospective study of 5,276 consecutive liveborn babies, 291 (5.5%) infants were diagnosed to have 473 congenital malformations. The incidence of major and minor malformations was 2.4 per cent and 3.1 percent respectively. Musculoskeletal defects accounted for 41.7 per cent of major anomalies. Among individual anomalies, congenital dislocation of hips, cleft lip±palate, microcephaly, club feet, polydactyly, hypospadias, Down syndrome and asymmetric crying facies had a frequency greater than 1 per 1000 livebirths. The incidence of neural tube defects was 3 per 1000 total births. The history of parental consanguinity was significantly higher among parents of infants with major congenital malformations as compared to unaffected control infants.     

Epidemiological Approaches to Identify Risk Factors for Human Congenital Malformations: Descriptive and Analytical Epidemiology of Cleft Lip and/or Palate in Japan*

Abstract This paper described three major epidemiological approaches to explore etiological clues to and risk factors for human congenital malformations, taking cleft lip and/or palate as an example. (1) An analysis of mortality statistics demonstrated an apparently downward trend of infant mortality from cleft lip and/or palate over the recent three decades in Japan. This particular finding was found to be plausibly ascribable to changing clinical assignment of causes of death from “cleft lip and/or palate” to “congenital heart diseases” or “multiple anomalies, syndromes or chromosome abnormalities”, when previous reports on incidence rate and autopsy series were examined. (2) A case-control study of 194 infants with cleft lip and/or palate (cases) and 194 normal infants (controls), who were matched to cases for sex, maternal age to within one year, birth order and residential area, yielded the following major findings, (a) A significantly increased risk was associated with parental highest educational attainment of less than 19 years, parental occupation of unskilled/service workers, positive family history of cleft lip and/or palate, positive past history of artificial abortion, maternal smoking habits at first trimester, and maternal episodes at first trimester of suffering from any diseases and of ingesting any drugs, (b) A significantly decreased risk was linked with frequent maternal intake at first trimester of such animal proteins as meats, fishes and shells, eggs and milk, (c) Maternal drinking habits and radiation exposures, and frequent maternal ingestion of Japanese/black tea were not associated. (d) Maternal coffee drinking at first trimester significantly elevated the risk, but turned to be unrelated when maternal smoking habits were statistically corrected. (3) A cohort study of approximately 10,000 pregnants, which is ongoing from April 1989 in Nagoya and aims to disclose the associations of parental life-style habits with general pregnancy outcomes including major congenital malformations, was briefly discussed.     

The Role of Medicine for Children with Developmental Disabilities*

Abstract The trend of the delivery of health care services for developmentally disabled children, especially those with congenital anomalies, is described. The importance of how the organization of community health services and the role of medicine and medical facilities mesh together in Japan is emphasized.