Clinical-epidemiologic assessment of pattern of birth defects associated with human teratogens: application to diabetic embryopathy

The concepts of sensitivity, specificity, and predictive value can be used to assess patterns of birth defects associated with human teratogens. Although sensitivity of any single defect is generally low for many known teratogens, the presence of specific defect combinations is usually predictive of the teratogen. To evaluate the patterns of birth defects associated with diabetic embryopathy, a sensitivity-specificity analysis was performed on 4929 infants with major defects ascertained by the population-based Metropolitan Atlanta Congenital Defects Program between 1968 and 1980. By reviewing hospital records, maternal insulin-dependent diabetes mellitus was confirmed in 26 infants. Patterns of defects were evaluated among infants born to mothers with insulin-dependent diabetes mellitus and compared with the rest of the Metropolitan Atlanta Congenital Defects Program case population. Multiple logistic regression analysis was used to assess defect combinations that predict for insulin-dependent diabetes mellitus. Of 26 infants, 8 had multiple defects. However, most defects and their combinations were poorly sensitive and predictive for insulin-dependent diabetes mellitus. The predictive value for insulin-dependent diabetes mellitus was greatest for the combination of vertebral and cardiovascular anomalies (6.5%). Also, several pathogenetic mechanisms were noted among patients with insulin-dependent diabetes mellitus, such as cell migration defects, cell death events, deformations, and cardiac flow lesions. The inability to find a clear-cut phenotype for diabetic embryopathy may be due to several etiologic factors and mechanisms associated with diabetic embryopathy.     

Risk for birth defects among premature infants: a population-based study

OBJECTIVE: To investigate the relationship between prematurity and birth defects. STUDY DESIGN: In a population-based cohort study, infants with birth defects were ascertained through the Metropolitan Atlanta Congenital Defects Program, a surveillance system with active methods of ascertainment. Gestational age data were obtained from birth certificates of liveborn, singleton infants with and without birth defects born in the 5-county metropolitan Atlanta area. RESULTS: Among 264,392 infants with known gestational ages born between 1989 and 1995, 7738 were identified as having birth defects (2.93%). Premature infants (<37 weeks' gestation) were more than two times as likely to have birth defects than term infants (37-41 weeks) (risk ratio = 2.43; 95% CI 2.30-2.56). This relationship was evident for several categories of birth defects. The rate of birth defects varied by gestational age categories, with the highest risk in the 29- to 32-week gestational age category (risk ratio = 3.37). CONCLUSIONS: The risk for birth defects is increased in premature infants. Awareness of this relationship is important for clinicians caring for premature infants. The morbidity and mortality associated with a particular defect may be significantly altered by the presence of prematurity. Further study of this association may provide insight into the etiology of these relatively common problems.     

Survival in infants with Down syndrome, Metropolitan Atlanta, 1979-1998

OBJECTIVE: Factors influencing survival among persons with Down syndrome (DS) are not well understood. We sought to evaluate survival of infants with DS and potential prognostic factors. STUDY DESIGN: Infants with DS who were born alive during 1979 to 1998 were identified using the Metropolitan Atlanta Congenital Defects Program (MACDP), a population-based surveillance system. To document vital status, we used data from hospital records, the National Death Index (NDI), and Georgia vital records. We estimated survival probability using the Kaplan-Meier product limit method and hazard ratios using a Cox proportional hazards model. RESULTS: Survival probability to 1 year was 92.9% (95% CI: 90.9-94.9) and to 10 years was 88.6% (95% CI: 85.0-92.2). Univariate analysis demonstrated that black maternal race, low birth weight, preterm birth, lower paternal education, presence of heart defects, and presence of other major congenital anomalies were important prognostic factors. After multivariate analysis, maternal race, presence of heart defects, low birth weight, and an interaction between maternal race and presence of heart defects were significantly associated with mortality risk. CONCLUSIONS: A racial disparity is apparent in survival for children with Down syndrome. Further study is needed to elucidate possible reasons for the racial disparity.     

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.     

Epidemiology of the early amnion rupture spectrum of defects

We used data from the population-based Metropolitan Atlanta Congenital Defects Program to study the epidemiology of the early amnion rupture spectrum of defects. For the period 1968 through 1982, we identified 45 patients among 388,325 live births, for a birth prevalence rate of 1.16 per 10,000. The prevalence for male infants was 0.91 and for female infants, 1.44. The defects occurred 1.76 times more often in blacks than in whites (95% confidence interval 0.98, 3.13). Infants of young, black multigravidas (less than 20 years, more than one pregnancy) showed the highest rate (6.2), and infants of older, black multigravidas showed the lowest rate (0.5) (rate ratio = 12.4, 95% confidence interval 4.2, 36.4). These findings suggest that young, black multigravidas are at much higher risk than are older, black multigravidas of having infants with this spectrum of defects. Ascertainment (diagnostic) differences between hospitals probably account for some of the racial discrepancy in birth prevalence, but they do not explain the maternal age effects in black multigravidas. Because the higher rates for blacks probably reflect more accurate diagnoses, the findings also suggest that a closer estimate of the true birth prevalence may be about 3 per 10,000 live births.     

Congenital Anomalies in Singapore

Abstract A 3-year study (Jan. 1986-Dec. 1988) in the Kandang Kerbau Hospital revealed 678 infants with birth defects in 44,842 livebirths, (15.13 per 1,000 live births, 95% confidence intervals, CI 14.0–16.2). There were 161 cases with musculoskeletal abnormalities (3.5 per 1,000, 95% CI 3.06-4.19), 111 gastrointestinal system malformations (2.47 per 1,000, 95% CI 2.04-2.58), 88 chromosomal abnormalities (1.96 per 1,000, 95% CI 1.57-2.42), 78 cardiovascular system abnormalities (1.74 per 1,000, 95% CI 1.38-2.17), 73 urogenital system defects (1.63 per 1,000, 95% CI 1.28-2.05), and 52 central nervous system defects (1.16 per 1,000, 95% CI 0.87-1.52). The prevalence of cleft lip, cleft palate, and cleft lip/palate was 1.72 per 1,000, and Down's Syndrome 1 in 700. At review, six weeks later, the false positive rate was 4% in the infants with defects, and in the group of 709 normal controls (matched by race, maternal age, ward class and time/date of birth), the false negative rate was 0.84%. The strongest risk factors were a family history of birth defects (odds ratio, OR 3.3, 95% CI 1.8-6.4), and previous abnormal sibling(s) (OR 2.4, 95% CI 1.1–5.3). Other risk factors included drug intake during pregnancy (OR 1.2, 95% CI 0.8-2.0), becoming significant with ingestion during the first trimester (OR 1.4, 95% CI 1.1-1.8). Traditional medicine (mainly Chinese herbs during pregnancy) had a slightly higher risk (OR 1.4, 95% CI 1.0–2.0). The National University Hospital keeps a register of birth defects; trained nurses interview all mothers using a set questionnaire. Evaluation of 11,460 livebirths over a 3-year period (1991–1993) revealed 472 cases (41.19 per 1,000 livebirths, 95% CI 37.48-44.90) with 171 musculoskeletal defects (14.92 per 1,000 livebirths, 95% CI 12.69-17.16), 105 cardiovascular defects (9.16 per 1,000, 95% CI 7.41-10.91), 64 urogenital defects (5.58 per 1,000, 95% CI 4.22-6.95), 30 gastrointestinal defects (2.62 per 1000, 95% CI 1.68-3.55), 35 mixed system defects (3.06 per 1,000, 95% CI 2.04-4.07), and 18 chromosomal abnormalities (1.57 per 1,000, 95% CI 0.85-2.30). The prevalence of cleft lip/cleft lip and palate was 1.48 per 1,000. This higher prevalence could be due to the present practice of routine screening of every infant on the first day of life, together with a careful assessment for musculoskeletal defects, especially congenital dislocation of the hips.     

Prevalence of birth defects among low-birth-weight infants. A population study

Major birth defects are diagnosed in about 3% to 4% of infants during their first year of life. Because many infants with birth defects have intrauterine growth retardation, are born prematurely, or both, the rate of birth defects undoubtedly varies according to the infant's birth weight. Nevertheless, the magnitude of such variation has not, to our knowledge, been adequately studied in well-defined populations. We analyzed data from the population-based Metropolitan Atlanta (Ga) Congenital Defects Program for 1978 through 1988. These data included information on 11,398 infants who were diagnosed with serious birth defects among 317,499 singleton live-born infants. Although the overall rate of birth defects was 3.6%, we observed a striking inverse relationship between the birth defects rate and the infants' birth weights. The birth defect rates were 16.2% for newborns weighing less than 1500 g at birth, 13.2% for newborns weighing from 1500 g to 1999 g, 6.2% for newborns weighing from 2000 g to 2499 g, 3.2% for newborns weighing from 2500 g to 3999 g, and 2.8% for newborns weighing 4000 g or more. Analyses by type of defect indicated that most birth defects were significantly associated with low birth weight. The higher risk of birth defects among low-birth-weight infants demonstrates that birth defects contribute to excess morbidity among low-birth-weight infants. Because of the overlap between birth defects and low birth weight, the prevention of low birth weight in the population depends greatly on a better recognition of the complex etiology of low birth weight and, in part, on the delineation of risk factors that influence the occurrence of birth defects.     

Cardiomyopathy and cardiomegaly in stillborn infants of diabetic mothers.

To report the incidence of cardiomegaly in stillborn normally formed infants of mothers with diabetes mellitus. This is a retrospective study with institutional ethics approval. The presence of cardiomegaly was recorded in stillborn infants of diabetic mothers (N = 27) and compared with that recorded in stillborn large-for-gestational age (LGA > 90th percentile, n = 18) and stillborn appropriately grown (10th to 90th percentiles, n = 107) nondiabetic infants. Blinded to the clinical details, the histology slides were reviewed to measure cardiac wall thickness and to record the presence or absence of myocardial fiber disarray. Stillborn infants of mothers with diabetes mellitus, when compared with appropriately grown stillborn nondiabetic infants and when adjusted for birth weight, had heavier hearts, thicker ventricular free wall measurements, and lighter brains. While cardiomegaly was reported in 22% of stillborn LGA infants, comparison with stillborn appropriately grown infants revealed no difference in heart weights corrected for birth weight. Comparison of LGA nondiabetic infants with stillborn diabetes mellitus infants revealed greater actual heart weight/expected for birth weight (P < 0.05) and lighter brains (actual brain weight/expected for birth weight, P < 0.05) in the diabetes mellitus group. Cardiomegaly is a common finding in stillborn infants of mothers with diabetes mellitus and may contribute to the risk of fetal death in these pregnancies.     

Does maternal cigarette smoking during pregnancy cause cleft lip and palate in offspring?

To investigate the relationship between maternal cigarette smoking and the risk of oral clefts in offspring, we examined data from the Atlanta Birth Defects Case-Control Study, which included 238 cases of cleft lip with or without cleft palate and 107 cases of cleft palate ascertained by the Metropolitan Atlanta Congenital Defects Program from 1968 through 1980. In all, 2809 infants who served as controls were frequency matched to cases by race, period of birth, and hospital of birth. Maternal periconceptional exposures to smoking were investigated through use of a structured questionnaire. Smoking exposure was defined as reported maternal smoking during the periconceptional period (from 3 months before conception to 3 months after pregnancy began). Offspring of smoking mothers were 1.6 and 2.0 times more likely than offspring of nonsmoking mothers to have isolated cleft lip with or without cleft palate and cleft palate, respectively. On the other hand, offspring of smoking mothers were not at increased risk of having cleft palate or cleft lip with or without cleft palate that are associated with other defects. Adjustment for potential confounding variables did not alter these results. A relatively modest effect of smoking may be explained by the presence of underlying etiologic heterogeneity in oral clefts and differential susceptibility to smoking. Because of the inconsistencies in the literature on the relationship between smoking and oral clefts, these results suggest the need to refine oral clefts into more homogeneous subgroups in epidemiologic studies of these defects.     

Predictors of breastfeeding non‐initiation in the NICU

This study compared predictors of breastfeeding non‐initiation between infants who were and were not admitted to the NICU so that interventions can target high‐risk mothers whose infants desperately need breastmilk. This was a population‐based retrospective cohort study of singleton Ohio live births using birth certificates, 2006–2015. In babies who were and were not admitted to the NICU, a multivariable logistic regression model assessed the association between breastfeeding non‐initiation and predictors relating to the mother, neonate, and labour and delivery events while adjusting for covariables. Of 1,463,506 births, 76,855 infants were admitted to the NICU (5.8% of study population), and breastfeeding was not initiated in 39.4% of them, compared with 31.5% of infants in the newborn nursery, p < 0.001. Apart from abnormal newborn conditions, smoking during pregnancy was the most significant risk factor for not breastfeeding in the NICU (RR 1.91 [95% CI 1.82–2.02]) and newborn nursery (RR 2.10 [95% CI 2.08–2.13]), followed by socioeconomic factors and multiparity. Limited prenatal visits (≤5) were a significantly higher risk factor in the NICU (RR 1.41 [95% CI 1.34–1.49]) than in the newborn nursery (RR 1.24 [95% CI 1.22–1.26]). Intentional home birth and use of infertility treatment were associated with breastfeeding initiation. The rate of breastfeeding initiation is lower in infants admitted to the NICU than those who are not, especially among mothers with limited prenatal care. Interventions should target mothers who smoke because they are least likely to breastfeed, and their babies, who are prone to serious health conditions, could especially benefit from breastmilk.     

Congenital malformations at birth — A prospective study from south India

Congenital malformations were studied prospectively from September 1989 to December 1992 covering 12,797 consecutive deliveries. The overall incidence of malformations was 3.7% and it was 3.2% among live births and 15.7% among still births. Three hundred and ninety seven birth defects were observed among 308 live births and 72 among 45 still births. The incidence of malformation was significantly higher among male babies (p <0.001), still births (p < 0.001), low birth weights (p < 0.001) and preterm babies (p < 0.001). Consanguinity among parents of malformed babies was more common (p < 0.001). Musculo-skeletal malformations were the commonest (9.69 per 1000) followed by cutaneous (6.33 per 1000), genitourinary (5.47 per. 1000), gastrointestinal (5.47 per 1000), central nervous system (3.99 per 1000) and cardiac anomalies (2.03 per 1000). Musculoskeletal, cutaneous and genitourinary malformations were common among live born babies while central nervous system and gastrointestinal defects were common among still born babies. Antenatal infections and ingestion of drugs were not found to be significant factors in the causation of birth defects.     

Perinatal outcome of infants born to diabetic mothers.

Two hundred and sixty three pregnant diabetic mothers' perinatal outcome was evaluated. Two hundred and twenty five infants were born to gestational diabetic mothers (IGDM) and 38 infants to mothers with established diabetes mellitus (IDM). In IGDM group, 34 babies (15%) were preterm and 45 (20%) were low birth weight (less than 2500 g). Thirty eight babies (17%) were large-for-dates (LFD) and 14 (6.2%) were small-for-dates (SFD). Among IDM group, 8 (21%) babies were preterm and 8 (21%) were low birth weight (less than 2500 g). Fifteen babies (39.5%) were LFD and 3 (8%) were SFD. Out of all babies, hypoglycemia occurred in 43 (16%), birth asphyxia in 24 (9%) and respiratory distress in 21 (8%). Nearly half of respiratory distress were due to hyaline membrane disease. Perinatal mortality rate was significantly higher (p less than 0.001) in IDM (237/1000 live birth) as compared to IGDM (40/1000 live birth).     

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.     

Morbidity during the first year of life in small for gestational age infants.

Postneonatal morbidity during infancy was studied in 284 small for gestational age (SGA) and 359 non-SGA term infants. None of these babies had congenital malformations and they were born to para 1 and para 2 mothers. SGA infants had an increased risk (OR: 1.7, 95% confidence interval: 1.1-2.6) of being admitted to hospital compared with non-SGA infants. The principal cause was respiratory tract infections. Increased hospitalisation among SGA infants was a factor only if the mother was a smoker-that is, smoked cigarettes at the time of conception. Among subgroups of SGA babies, there was an increased risk for infants of non-repeaters (women without a previous SGA child) (OR: 2.4, 95% CI: 1.4-3.8) and for infants with symmetric (OR: 2.0, 95% CI: 1.2-3.3) body proportions compared with non-SGA infants. The results suggest that, beginning in early pregnancy, growth retardation may have long term consequences for subsequent infant morbidity, particularly if the mother is smoker.     

Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes

BACKGROUND: Diabetes type 1 is associated with an increased risk for infant congenital malformations. It is debated whether this is true also at gestational diabetes. AIMS: To study occurrence of congenital malformations in infants whose mothers had preexisting or gestational diabetes. STUDY DESIGN: A register study covering over 1.2 million Swedish births in 1987-1997 based on the Swedish health registries. SUBJECTS: We identified from the Medical Birth Registry 3864 infants born of women with preexisting diabetes and 8688 infants born of women with gestational diabetes. OUTCOMES MEASURES: Congenital malformations identified in the Medical Birth Registry, the Registry of Congenital Malformations, and the Hospital Discharge Registry. The rates of congenital malformations among these infants was compared with the population rates. RESULTS: At preexisting diabetes, the total malformation rate was 9.5% while the rate at gestational diabetes was similar to the population rate, 5.7%. At preexisting diabetes, certain conditions were more common than expected: orofacial clefts, cardiovascular defects, oesophageal/intestinal atresia, hypospadias, limb reduction defects, spine malformations, and polydactyly. For some of these conditions, an excess was found also for infants whose mothers had gestational diabetes. Infants with multiple malformations were in excess at preexisting diabetes but not at gestational diabetes but the specific type of malformations involved were similar in the two diabetes groups. CONCLUSIONS: It is suggested that in the group of gestational diabetes exists a subgroup with an increased risk for a diabetes embryopathy, perhaps due to preexisting but undetected diabetes type 2.     

The changing epidemiology of neural tube defects. United States, 1968-1989.

OBJECTIVE--To describe the recent trends and epidemiologic characteristics of neural tube defects in the United States. RESEARCH DESIGN--Ongoing surveillance data. SETTING--Two birth defect surveillance systems: the nationwide Birth Defects Monitoring Program and the Metropolitan Atlanta (Ga) Congenital Defects Program for 1970 through 1989 and 1968 through 1989, respectively. PARTICIPANTS--Between 1970 and 1989, using discharge diagnoses of approximately 1 million live-born and stillborn infants per year, the Birth Defects Monitoring Program identified 15,503 cases of spina bifida and anencephaly. Between 1968 and 1989, using discharge diagnoses and clinical records until age 1 year of 38,000 infants per year, the Metropolitan Atlanta Congenital Defects Program identified 800 cases of spina bifida and anencephaly. INTERVENTIONS--None. MEASUREMENTS/MAIN RESULTS--Nationwide, neural tube defect rates have declined from 1.3 per 1000 births in 1970 to 0.6 per 1000 births in 1989. In Atlanta, neural tube defect rates have declined from 2.0 per 1000 births in 1968 to 0.6 per 1000 births in 1989. Several changes in the epidemiologic characteristics of neural tube defects were observed: (1) the proportion of spina bifida cases has increased; (2) the proportion of neural tube defect cases compared with the proportion of other unrelated defects has increased; (3) the race ratio of whites to other races for isolated neural tube defect cases has declined in Atlanta; and (4) the rate of isolated neural tube defects in females has also decreased. CONCLUSIONS--The declining rates of neural tube defects can be partially explained by increased widespread prenatal diagnostic techniques, strongly suggesting the role of environmental factors in neural tube defects. In particular, the use of multivitamins and folic acid to prevent the occurrence of neural tube defects needs further evaluation. Nevertheless, the changing clinical and epidemiologic characteristics of cases over time points to the etiologic heterogeneity of these conditions.     

SGA subtypes and mortality risk among singleton births

OBJECTIVES: To determine whether early mortality (first year of life) risks among small for gestational age (SGA) neonates were similar regardless of SGA subtype based on three chronological classifications (term, preterm and post-term). STUDY DESIGN: Retrospective cohort study on all singleton live births in the United States from 1995 to 1999 inclusive. Adjusted risk estimates were computed from logistic regression models using non-SGA infants as the referent. RESULTS: When SGA infants were compared as a homogeneous entity to non-SGA infants, the risks for infant, neonatal and post-neonatal mortality were significantly greater in SGA infants [AOR (adjusted odds ratio)=3.0, 95% CI (confidence interval)=2.9-3.0 for infant mortality; AOR=3.2, 95% CI=3.1-3.2 for neonatal mortality; and AOR=2.6, 95% CI=2.6-2.7 for post-neonatal mortality]. However, heterogeneity existed in terms of mortality risk thresholds across SGA babies. The most remarkable risk magnitude was observed among preterm SGA infants [infant mortality AOR=13.8, 95% CI=13.6-14.1; neonatal death AOR=17.4, 95% CI=17.0-17.7; and post-neonatal death AOR=7.4, 95% CI=7.1-7.6]. The adjusted odds ratio for term and post-term SGA infants were comparable regardless of the period during infancy, and were much less than those observed for preterm SGA infants. CONCLUSIONS: SGA is a heterogeneous disease in terms of prognosis for survival. Preterm SGA infants bear an extremely high risk for mortality during infancy, and counseling of affected parents should reflect this risk divergence.     

Descriptive epidemiology of hemivertebrae, Hawaii, 1986-2002

The intent of this study was to report on the epidemiology of hemivertebrae. Cases were derived from a population-based birth defects registry in Hawaii and comprised all infants and fetuses with hemivertebrae delivered during 1986-2002. Hemivertebrae rates per 10 000 births were determined for selected factors and comparisons made by calculating the rate ratio (RR) and 95% confidence interval (CI). Forty-two cases of hemivertebrae were identified, for a total rate of 1.33. Forty-one of the cases were live births, of which 26.83% expired within one year after delivery. Other major structural birth defects were found in 95.24% of the cases. The most frequent associated defect was scoliosis, affecting 54.76% of the cases. The rate among females was significantly lower than among males (RR 0.48, 95% CI 0.23-0.94). The rate was lower with maternal age > or =35 years (RR 0.50, 95% CI 0.10-1.57) and higher with birth weight < 2500 g (RR 5.96, 95% CI 2.84-11.90) and gestational age < 38 weeks (RR 3.94, 95% CI 2.01-7.64). The majority of hemivertebrae cases had other major structural birth defects. Hemivertebrae occurred predominantly among males and risk was lower with increased maternal age. Rates for hemivertebrae were higher with lower birth weight and gestational age. Further population-based research involving larger study populations are recommended to confirm these observations.     

Pregnancy outcomes in mothers with pregestational diabetes: a population-based study in North Rhine (Germany) from 1988 to 1993

The purpose of this study was to estimate the proportion of pregnancies with pregestational diabetes in Germany, to compare the outcome of these pregnancies to pregnancies in nondiabetic mothers and to identify risk factors for poor pregnancy outcomes in mothers with pregestational diabetes. Data of the “Perinatalerhebung Nordrhine” from 1988–1993 were analysed. The Perinatalerhebung is an ongoing quality assurance programme of prenatal and perinatal care in the region of North Rhine (South Western part of North Rhine-Westphalia). During the observation period a proportion of 93%–100% of the annual births in the region (n = ∼100000) were included in the study. Their data had been documented by the obstetricians in a standard multiple choice questionnaire. The outcome parameters perinatal mortality, macrosomia, prematurity, and malformations were analysed in relation to several defined explanatory variables. There were 2,402 births in mothers with pregestational diabetes (0.4% of all births). The proportions of poor pregnancy outcomes in women with pregestational diabetes were 2.8% for perinatal mortality, 27.6% for macrosomia, 21.1% for prematurity and 2.1% for malformations . The respective relative risks compared to the non diabetic mothers were 4.3 (95% CI 3.4–5.5) for perinatal mortality, 3.1 (95% CI 2.9–3.3) for macrosomia, 2.7 (95% CI 2.5–2.9) for prematurity and 1.7 (95% CI 1.3–2.3) for malformations . The main risk factor for perinatal mortality in children of diabetic mothers after adjustment for maternal smoking, ethnicity, parents' professional achievement, type of obstetric hospital, and maternal age was substandard use of prenatal care. Conclusions The prevalence of births from mothers with pregestational diabetes and their pregnancy outcomes were similar to those in other Western countries. The standard for non-diabetic mothers has not been reached yet. Further improvements may be achieved if all diabetic women are convinced to use the standard prenatal care facilities throughout pregnancy. Received: 3 February 1997 / Accepted: 26 May 1997