Cardiovascular malformations among preterm infants.
OBJECTIVE
Preterm birth and cardiovascular malformations are the 2 most common causes of neonatal and infant death, but there are no published population-based reports on the relationship between them. We undertook this study to determine the prevalence and spectrum of cardiovascular malformations in a preterm population, the prevalence of prematurity among infants with cardiovascular malformations, and the influence of prematurity and cardiovascular malformations on outcomes.


METHODS
We based the study on the population of the former Northern Health Region of England. We identified all live-born infants with cardiovascular malformations diagnosed in the first 1 year of life from the regional pediatric cardiology database, which includes the gestational age and details of the diagnosis. We limited ascertainment to malformations diagnosed by the age of 12 months. Infants with isolated patent ductus arteriosus or atrial septal defect were excluded, to avoid ascertainment bias. Infants with ventricular septal defect were classified according to whether they required surgery in the first 1 year. There are no population data on gestational ages for all births in our population for the era of this study; therefore, we used data published in the literature for populations similar to our own to predict that 0.4% of live births occur at <28 weeks of gestation, 0.9% at 28 to 31 weeks, and 6% at 32 to 36 weeks. Overall, 7.3% of live-born infants are preterm.


RESULTS
Of 521619 live-born infants in 1987-2001, 2964 had cardiovascular malformations (prevalence: 5.7 cases per 1000 live births). Cardiovascular malformations were present at 5.1 cases per 1000 term infants and 12.5 cases per 1000 preterm infants. The odds ratio (OR) for a cardiovascular malformation in prematurity was 2.4 (95% confidence interval [CI]: 2.2-2.7). We found that 474 infants (16%) with cardiovascular malformations were born at <37 weeks of gestation, giving an OR for prematurity among infants with a cardiovascular malformation of 2.4 (95% CI: 2.2-2.7). More infants were born preterm with diagnoses of pulmonary atresia with ventricular septal defect (23%), complete atrioventricular septal defect (22%), and coarctation of the aorta, tetralogy of Fallot, and pulmonary valve stenosis (each 20%). Fewer were born preterm with diagnoses of pulmonary atresia and intact ventricular septum (7%), transposition of the great arteries (8%), and single ventricle (9%). We found that 18% of infants with ventricular septal defect requiring surgery were preterm, compared with 13% in the nonsurgical group. Preterm infants with ventricular septal defect required surgery in 30% of cases, compared with 23% of term infants with ventricular septal defect. These figures show that the excess of cardiovascular malformations among preterm infants cannot be explained by greater ascertainment of minor ventricular septal defects. In our denominator population, 646 live-born infants were recognized as having trisomy 21, and gestational age data were available for 609. Of these, 149 (25%; 95% CI: 21-28%) were preterm. Approximately two thirds of infants with complete atrioventricular septal defect have trisomy 21. Complete atrioventricular septal defect was no more common among preterm infants with trisomy 21 (16%) than among term infants with trisomy 21. However, the increased incidence of prematurity among infants with trisomy 21 probably explains some of the excess of preterm births among infants with complete atrioventricular septal defect. Only 4 (11%) of 38 infants with 22q11 deletion were born preterm. None of those infants had pulmonary atresia with ventricular septal defect; therefore, 22q11 deletion does not explain the excess of preterm births in pulmonary atresia with ventricular septal defect. The OR for death in the first 1 year in the presence of a cardiovascular malformation was 4.4 (95% CI: 3.1-5.5) overall; ORs were 1.8 at <28 weeks of gestation, 3.7 at 28 to 31 weeks, 11.0 at 32 to 36 weeks, and 35.6 at term.


CONCLUSIONS
This study showed that preterm infants have more than twice as many cardiovascular malformations as do infants born at term and that 16% of all infants with cardiovascular malformations are preterm. It also showed, not surprisingly, that there is an increased mortality rate among infants born preterm with a cardiovascular malformation. The additional effect of cardiovascular malformations on mortality rates is most marked for term and near-term infants, for whom mortality rates are otherwise low. The excess of cardiovascular malformations among preterm infants is intriguing but not easy to explain. Previous studies of birth weight among infants with cardiovascular malformations reported a significant increase in the likelihood of being small for gestational age among infants with tetralogy of Fallot, complete atrioventricular septal defect, hypoplastic left heart, or large ventricular septal defect. There is an obvious relationship between birth weight and gestational age, and those studies also showed an increased prevalence of prematurity among infants with tetralogy of Fallot, pulmonary stenosis, aortic stenosis, coarctation of the aorta, complete atrioventricular septal defect, or ventricular septal defect. There is also a high prevalence of cardiovascular malformations among late stillbirths, with major differences in the number and spectrum of cardiovascular malformations, compared with those seen in postnatal life. In particular, there is a greater incidence of coarctation of the aorta, double-inlet left ventricle, hypoplastic left heart, truncus arteriosus, double-outlet right ventricle, and atrioventricular septal defect among stillbirths. This spectrum of malformations is similar to that in our study and to those in other reports. Whether the increased prevalence of cardiovascular malformations among preterm infants and the increase in stillbirths suggest clues to the cause is difficult to say. The influence of preterm birth should be taken into account in risk assessment and risk stratification for surgical repair.
Tanner
Kirsty
K
Department of Paediatric Cardiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Sabrine
Nilofer
N
Wren
Christopher
C
D006330:Heart Defects, Congenital / Q000453:epidemiology*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000453:epidemiology*; D015995:Prevalence