Acta Pcediatr Scand 80: 21 8-225, 1991
Pre- and Perinatal Factors in Febrile Convulsions L. FORSGREN, R. SIDENVALL, H. K:SON BLOMQUIST, J. HEIJBEL and L. NYSTROM From the Department of Neurology, University Hospital, Umed, Sweden, the Department of Paediatrics, University Hospital, Umed, Sweden and the Department of Epidemiology and Health Care Research, Umed University, Umed, Sweden ABSTRACT. Forsgren, L., Sidenvall, R., Blomquist, H. Kxon, Heijbel, J. and Nystriim, L. (Departments of Neurology, Paediatrics and Epidemiology and Health Care Research, University Hospital, Umeii, Sweden). Acta Paediatr Scand 80: 218, 1991.
In a community based study, 110 children with febrile convulsions (FC) were identified prospectively. Pre- and perinatal risk factors were compared with 213 age and sex matched controls sampled from the community. During pregnancy, proteinuria and preeclampsia/eclampsia Occurred more often in mothers of cases. Premature birth and bilirubinemia > 200 pmol/l were also more common in cases. There were no differences between cases and controls in Occurrence of chronic illnesses in mothers, parents age at birth, birth order, and factors occurring during delivery such as type of anesthesia, Occurrence of acute or elective cesarean section, use of vacuum extraction, mode of presentation, signs of fetal distress in amnion fluid, umbilical problems, abnormalities of fetal heart rate or duration of delivery. Perinatal asphyxia was uncommon and there was no difference between cases and referents. Occurrence of complications during the first neonatal week did not differ between groups. Key words: febrile convulswns, epidemiology, case-control, risk factors, prenatal, perinatal.
The relation between pre- and perinatal factors and febrile convulsions (FC) is obscure. In the study of Van den Berg & Yerushalmy (1) abnormalities during gestation were comparable in children affected and not affected by FC, but in other studies were more common among cases (2, 3). Breech deliveries were comparable with controls in one study (2) but in another study breech deliveries were more common in children affected by FC (4). Prematurity was reported to be more common in children with FC compared to t 6 general population by Degen & Goller (9,but not by Van den Berg & Yerushalmy (1). Low birthweight has been reported in two studies as more common in children with FC than in controls (2, 4), but no difference was found in another study (1). Several studies which have assessed pre- and perinatal factors did not have a control group. The different results may be an effect of differences in the selection of children with FC. Most studies which have assessed risk factors for FC were hospital based, which may have caused a selection of more severe cases. The present study was community-based and used incident cases, prospectively identified, in order to minimize selection bias and avoid missing mild cases (6). The aim of the present study was to exploratively assess the association of different pre- and perinatal factors with the occurrence of newly diagnosed FC. MATERIAL AND METHODS Study area and population. The county of Vasterbotten is located in northern Sweden. On December 31, 1986 there were 21 744 children in the age-group 0-6 years, 11 092 boys and 10652 girls. A detailed description of the study area is given elsewhere (7).
Pre- and perinatal factors in febrile convulsions 2 I9
Acta Paediatr Scand 80
Sources. All district nurses and doctors in the county who were anticipated to get in contact with patients with seizures in the area studied, were requested to report or refer all patients with a newly diagnosed or suspected seizure disorder. It was explicitly stated that this also included children with FC. This information as well as a brief background and the reasons for the study were given in a letter two weeks before the start of the study and every fourth month during the study peliod. The procedure has been described in more detail elsewhere (7). Cases and controls. All children below age 7 years, residents in the study area and who had their first FC diagnosed during the study period (Nov. 1 , 1985 to June 30, 1987), were included. For each case, two age- and sex-matched referents from the county were traced using the official Swedish population register (SPAR-DAFA). Definitions. All children below age 7 who developed their first seizure, focal or generalized, during a febrile illness were considered to have FC. Children who had earlier had one or several afebrile seizures and children with signs of cerebral infection or intoxication, were excluded. A febrile seizure was designated as complicated if the duration of the seizure was 30 min or longer, or if there were focal (partial) components of the seizure, or if there were postictal phenomena which either indicated a focal seizure (e.g. Todd’s paralysis) or a more generalized affection of the nervous system (e.g. ataxia 24-48 hours following the seizure), or if there were repeated seizures during the 24 hours following the first FC. A mother was considered hypertensive if the blood pressure on two separate occasions was 2 140 systolic or 3 90 diastolic. Maternal proteinuria 2 1 g/l was noted. Data collection procedure. Children who had suspected FC diagnosed for the first time during the study period, were evaluated by a paediatrician and, on the basis of the history, clinical examination and, sometimes, laboratory investigations, they were judged to have hadhot to have had FC. Obstetrical records of cases and referents were reviewed blindly (by L. F.) and paediatric medical records were reviewed non-blindly (by L. F. and J. H.). The information of interest was transferred to a structured questionnaire. The study was prospective in the sense that cases with FC were prospectively identified, and retrospective in the sense that pre- and perinatal events for these prospectively identified cases (and controls) were analyzed retrospectively. The obstetric and paediatric records of 110 of the 1 1 5 cases were evaluated. The records were not traceable in 2 cases and in 3 cases the parents denied access to records for this investigation. Among controls, 213 of the 230 obstetrical records were evaluated. The records of 7 controls were not traceable and the parents to 10 of the controls denied access to records. A paediatric record existed for 177 of the 230 controls, and 166 of these were evaluated. Of the 110 cases whose medical records were evaluated, 6OYo were boys and 40Yo girls. The corresponding figures for the 231 controls were 62% and 38% respectively. Through a question-
Table 1. Smallest detectable relative risk (R)for one-sided significance test with 110 cases and 2 controls per case a = type I error, P = Power = 1-8 = 1-type I1 error, Pr = proportion of control group exposed
a
Pr
0.90
0.80
0.05 0.10 0.25 0.50 0.75 0.05 0.10 0.25 0.50 0.75
3.41 2.62 2.08 2.00 2.48 2.81 2.23 1.82 1.75 2.04
3.01 2.36 1.91 1.84 2.18 2.46 2.00 1.67 1.61 1.81
~
0.01
0.05
220 L. Forsgren et al.
Acta Paediatr Scand 80
naire additional information was collected on 92 Yo (n= 101) of the cases and 89 Yo (n= 189) of the controls. Statistical analysis. The proportion of missing answers for a question are only presented in tablep if > 10%of the answers were missing or there were a significant difference between cases and referents. When analysing data from the study the matching was dissolved since ratios between the relative riskfrom matched and unmatched data were close to one (8). The relative risks were estimated by odds ratios (OR) and pvalues calculated according to Miettinen (9). To be able to estimate whether the differences of the mean between cases and controls for different risk factors were due to chance or not, Student’s t-test was applied. The exposure to different possible risk factors varies as a function of the proportion of exposed among the referents. Table 1 illustrates for a one-sided significance test the smallest detectable relative risk for n = 110 cases provided two controls per case, a type I error of 0.01 and 0.05 and a type I1 error of 0.10 or 0.20. This means that for a certain risk factor with 10% of the controls exposed and given 110 cases and 220 controls and a type I error of 0.05, this study has a power of 8OYo to detect a relative risk of 2.00, i.e. an overrisk of 100%(10). Logistic regression was applied to analyze the effect of all variables that were of major importance in the bivariate analysis (p60.05) or had been suggested to be important in the literature. The software EPILOG uses the Newton-Raphson interactive technique to obtain maximum likelihood estimates of the coefficients (1 1). Approval. The study was approved by the Ethics committee of Umea University Hospital and by the Swedish Data Inspection Board.
RESULTS
Fathers’ age at birth of caselreferent. There was no statistically significant difference in the mean age between fathers of cases and fathers of controls. , , Characteristics of mothers. Chronic illnesses (hypertension, heart disease, renal disease, epilepsy) were uncommon in mothers of cases and controls and no differ*ences were found. Diabetes mellitus, alcohol/drug abuse and malformations were not found in any mother. The occurrence of spontaneous abortions and stillbirths in prior pregnancies were similar in both groups. During the pregnancy/delivery, the civil status and presence of pelvic contraction did not differ between mothers of cases and controls. There was no difference between cases and controls in birth order and age of the mothers at birth of cases or controls. Of the cases, 45.5% were first born and among controls, 37.6% (OR= 1.35; p=0.25). Table 2. Events during the gestation of cases with FC (n= 10) and controls (n=213), (%). Odds ratio (OR) and p-values Frequency (Yo) Events during gestation
Cases
Controls
OR
P
Onset of hypertension Proteinuria Weight increase > 2 kglweek Maternal diabetes mellitus Colitis, proctitis, Morbus Crohn Hyperemesis Epileptic seizure Toxicosis Pre-eclampsia Eclampsia Toxicosis or pre-eclampsia Preeclampsia or eclampsia
13.6 7.3 0 6.4 2.7 2.7 0 9.1 2.7 0.9 11.8 3.6
7.5 0.9 0.5 2.8 0 0.5 0.5 6.6 0 0 6.6 0
1.90 8.04
0.13 0.01 0.74 0.32 0.07 0.23 0.73 0.58 0.07 0.74 0.17 0.02
2.00 5.94 1.40 1.88
Pre- and perinatal factors in febrile convulsions 22 1
Acta Paediatr Scand 80
Pregnancy. Table 2 shows the distribution of events that occurred during the gestation. Proteinuria occurred more often in mothers of cases. Pre-eclampsia or eclampsia were more common in mothers of cases, although both were rare events. There were no differences between groups regarding the occurrence of twin pregnancies, anemia, vaginal bleeding, placenta praevia, ablatio placentae, infections, maternal diabetes mellitus, epileptic seizures, surgery, diagnostic amniocentesis, drug consumption, alcohol abuse and smoking. Delivery characteristics. There were no differences between cases and controls with respect to factors occurring during delivery. The following factors were investigated: type of anesthesia, use of surgical or medical induction, Cesarean section, use of forceps or vacuum extraction, mode of presentation, meconium staining and obnoxious smell of amnion fluid, placental and umbilical abnormalities and duration of delivery. The fetal heart rate was monitored and related to uterine contractions by cardiotocogram in 56% of cases and 57% of controls. Abnormalities such as tachycardia > 160, bradycardia < 100 for more than 1 min, decreased variability and latehariable decelerations were equally common in cases and controls. Meconium staining of amnion fluid, another sign of prenatal asphyxia, were also equally distributed between groups. Gestational age and birthweight. When birth characteristics were investigated it was found that cases were more often born preterm (Table 3). Mean gestational age at birth was 38.6 weeks (SD=2.2) for cases and 39.2 weeks (SD= 1.8) for referents (Student’s t-test, p=O.OI). The mean birthweight of cases was 3.438 kg (SD=0.55) and of controls 3.562 kg (SD =0.60). The difference was not statistically significant (Student’s t-test: p=O.O6). Neonatal characteristics. Most children spent 5-7 days at the hospital. During this period there were no differences between groups in occurrence of respiratory disorders, heart disease, affections of the central nervous system and malformations. Laboratoryfindings. The mean gestational age of cases and controls with serum bilirubin > 200 pmol/l was lower than for cases and controls with normal bilirubin (cases: 36.7 vs. 39.1 weeks, p 41 complete weeks < 38 complete weeks < 37 complete weeks Child characteristics Birthweight < 2 500 g Small for gestational age Large for gestational age Apgar score < 6 at 1 min Apgar score < 6 at 5 min 15-918302
Cases
Controls
OR
p
1.8 19.1 13.6
1.4 10.8 4.7
1.29 1.94 3.19
0.82 0.06 0.01
8.2 1.8 2.7 6.4 0.9
4.2 0.9 7.0 2.3 0.9
1.96 1.89 0.36 2.84 1.05
0.25 0.88 0.16 0.13 0.57
222 L. Forsgren et al.
*
Acta Paediatr Scand 80
tional weeks and of the 20 controls with hyperbilirubinemia (>200 pmol/l), 7 (35%) were born before 37 completed gestational weeks. Thus, the more common occurrence of hyperbilirubinemia in cases is partly explained by a larger proportion of prematurity among cases compared with controls. Hence, when only the cases and referents born 3 37 completed gestational weeks were compared, no statistically significant difference was found (Table 4). Significantly more cases than controls had hyperbilirubinemia of such a degree that it warranted treatment (phototherapy or blood exchange transfusion). One child (case) had a serum bilirubin of 172 pmol/l but was treated with phototherapy because of profound prematurity (30 weeks). When the 1 1 children with a serum bilirubin > 300 pmol/l were compared, no difference between groups were found (odds ratio 3.55; p=0.07). There was no difference between groups in the occurrence of hypoglycemia and hypocalcemia. Complications combined. In order to compare the pre- and perinatal variables assessed by Heijbel et al. (3), occurrence of one or more of the following was cornpared between groups: maternal diabetes mellitus or essential hypertension, pre-eclampsia, vaginal bleedings, cesarean section, vacuum extraction, breech delivery, second twin, birthweight 342 pmol/l and congenital heart disease. At least one complication occurred in 49% of cases and 41 % of controls. Two or more complications occurred in 16% of cases and controls. The difference between groups was not statistically significant (OR= 1.37; 95 Yo confidence limits 0.86, 2.18). Two variables were included in the model (pt0.05)when stepwise logistic regression was applied on all variables that were statistically significant in the bivariate analysis or had been suggested to be of importance in the literature. These were gestational age < 37 complete weeks and other than normal mode of presentation at delivery.
DISCUSSION Wallace (12) found, in a hospital-based study, that mothers of children with FC more often suffered from chronic medical illnesses than mothers of controls and that mothers to males with FC were subfertile in an interval of 1-2 years preceding and following birth of the child with FC. No such difference was found in the Table 4. Hyperbilirubinemia, hypoglycemia and hypocalcemia of cases with FC and controls (%). Odds ratio (OR) and p-values Frequency (Yo) Variables
Cases
Controls
OR
p
Hyperbilirubinemia Hyperbilirubinemia and 2 37 weeks Hyperbilirubinemia and < 37 weeks" Treated hyperbilirubinemia Treated hyperbilirubinemiaand 3 37 weeks Treated hyperbilirubinemiaand
Pre- and Perinatal Factors in Febrile Convulsions L. FORSGREN, R. SIDENVALL, H. K:SON BLOMQUIST, J. HEIJBEL and L. NYSTROM From the Department of Neurology, University Hospital, Umed, Sweden, the Department of Paediatrics, University Hospital, Umed, Sweden and the Department of Epidemiology and Health Care Research, Umed University, Umed, Sweden ABSTRACT. Forsgren, L., Sidenvall, R., Blomquist, H. Kxon, Heijbel, J. and Nystriim, L. (Departments of Neurology, Paediatrics and Epidemiology and Health Care Research, University Hospital, Umeii, Sweden). Acta Paediatr Scand 80: 218, 1991.
In a community based study, 110 children with febrile convulsions (FC) were identified prospectively. Pre- and perinatal risk factors were compared with 213 age and sex matched controls sampled from the community. During pregnancy, proteinuria and preeclampsia/eclampsia Occurred more often in mothers of cases. Premature birth and bilirubinemia > 200 pmol/l were also more common in cases. There were no differences between cases and controls in Occurrence of chronic illnesses in mothers, parents age at birth, birth order, and factors occurring during delivery such as type of anesthesia, Occurrence of acute or elective cesarean section, use of vacuum extraction, mode of presentation, signs of fetal distress in amnion fluid, umbilical problems, abnormalities of fetal heart rate or duration of delivery. Perinatal asphyxia was uncommon and there was no difference between cases and referents. Occurrence of complications during the first neonatal week did not differ between groups. Key words: febrile convulswns, epidemiology, case-control, risk factors, prenatal, perinatal.
The relation between pre- and perinatal factors and febrile convulsions (FC) is obscure. In the study of Van den Berg & Yerushalmy (1) abnormalities during gestation were comparable in children affected and not affected by FC, but in other studies were more common among cases (2, 3). Breech deliveries were comparable with controls in one study (2) but in another study breech deliveries were more common in children affected by FC (4). Prematurity was reported to be more common in children with FC compared to t 6 general population by Degen & Goller (9,but not by Van den Berg & Yerushalmy (1). Low birthweight has been reported in two studies as more common in children with FC than in controls (2, 4), but no difference was found in another study (1). Several studies which have assessed pre- and perinatal factors did not have a control group. The different results may be an effect of differences in the selection of children with FC. Most studies which have assessed risk factors for FC were hospital based, which may have caused a selection of more severe cases. The present study was community-based and used incident cases, prospectively identified, in order to minimize selection bias and avoid missing mild cases (6). The aim of the present study was to exploratively assess the association of different pre- and perinatal factors with the occurrence of newly diagnosed FC. MATERIAL AND METHODS Study area and population. The county of Vasterbotten is located in northern Sweden. On December 31, 1986 there were 21 744 children in the age-group 0-6 years, 11 092 boys and 10652 girls. A detailed description of the study area is given elsewhere (7).
Pre- and perinatal factors in febrile convulsions 2 I9
Acta Paediatr Scand 80
Sources. All district nurses and doctors in the county who were anticipated to get in contact with patients with seizures in the area studied, were requested to report or refer all patients with a newly diagnosed or suspected seizure disorder. It was explicitly stated that this also included children with FC. This information as well as a brief background and the reasons for the study were given in a letter two weeks before the start of the study and every fourth month during the study peliod. The procedure has been described in more detail elsewhere (7). Cases and controls. All children below age 7 years, residents in the study area and who had their first FC diagnosed during the study period (Nov. 1 , 1985 to June 30, 1987), were included. For each case, two age- and sex-matched referents from the county were traced using the official Swedish population register (SPAR-DAFA). Definitions. All children below age 7 who developed their first seizure, focal or generalized, during a febrile illness were considered to have FC. Children who had earlier had one or several afebrile seizures and children with signs of cerebral infection or intoxication, were excluded. A febrile seizure was designated as complicated if the duration of the seizure was 30 min or longer, or if there were focal (partial) components of the seizure, or if there were postictal phenomena which either indicated a focal seizure (e.g. Todd’s paralysis) or a more generalized affection of the nervous system (e.g. ataxia 24-48 hours following the seizure), or if there were repeated seizures during the 24 hours following the first FC. A mother was considered hypertensive if the blood pressure on two separate occasions was 2 140 systolic or 3 90 diastolic. Maternal proteinuria 2 1 g/l was noted. Data collection procedure. Children who had suspected FC diagnosed for the first time during the study period, were evaluated by a paediatrician and, on the basis of the history, clinical examination and, sometimes, laboratory investigations, they were judged to have hadhot to have had FC. Obstetrical records of cases and referents were reviewed blindly (by L. F.) and paediatric medical records were reviewed non-blindly (by L. F. and J. H.). The information of interest was transferred to a structured questionnaire. The study was prospective in the sense that cases with FC were prospectively identified, and retrospective in the sense that pre- and perinatal events for these prospectively identified cases (and controls) were analyzed retrospectively. The obstetric and paediatric records of 110 of the 1 1 5 cases were evaluated. The records were not traceable in 2 cases and in 3 cases the parents denied access to records for this investigation. Among controls, 213 of the 230 obstetrical records were evaluated. The records of 7 controls were not traceable and the parents to 10 of the controls denied access to records. A paediatric record existed for 177 of the 230 controls, and 166 of these were evaluated. Of the 110 cases whose medical records were evaluated, 6OYo were boys and 40Yo girls. The corresponding figures for the 231 controls were 62% and 38% respectively. Through a question-
Table 1. Smallest detectable relative risk (R)for one-sided significance test with 110 cases and 2 controls per case a = type I error, P = Power = 1-8 = 1-type I1 error, Pr = proportion of control group exposed
a
Pr
0.90
0.80
0.05 0.10 0.25 0.50 0.75 0.05 0.10 0.25 0.50 0.75
3.41 2.62 2.08 2.00 2.48 2.81 2.23 1.82 1.75 2.04
3.01 2.36 1.91 1.84 2.18 2.46 2.00 1.67 1.61 1.81
~
0.01
0.05
220 L. Forsgren et al.
Acta Paediatr Scand 80
naire additional information was collected on 92 Yo (n= 101) of the cases and 89 Yo (n= 189) of the controls. Statistical analysis. The proportion of missing answers for a question are only presented in tablep if > 10%of the answers were missing or there were a significant difference between cases and referents. When analysing data from the study the matching was dissolved since ratios between the relative riskfrom matched and unmatched data were close to one (8). The relative risks were estimated by odds ratios (OR) and pvalues calculated according to Miettinen (9). To be able to estimate whether the differences of the mean between cases and controls for different risk factors were due to chance or not, Student’s t-test was applied. The exposure to different possible risk factors varies as a function of the proportion of exposed among the referents. Table 1 illustrates for a one-sided significance test the smallest detectable relative risk for n = 110 cases provided two controls per case, a type I error of 0.01 and 0.05 and a type I1 error of 0.10 or 0.20. This means that for a certain risk factor with 10% of the controls exposed and given 110 cases and 220 controls and a type I error of 0.05, this study has a power of 8OYo to detect a relative risk of 2.00, i.e. an overrisk of 100%(10). Logistic regression was applied to analyze the effect of all variables that were of major importance in the bivariate analysis (p60.05) or had been suggested to be important in the literature. The software EPILOG uses the Newton-Raphson interactive technique to obtain maximum likelihood estimates of the coefficients (1 1). Approval. The study was approved by the Ethics committee of Umea University Hospital and by the Swedish Data Inspection Board.
RESULTS
Fathers’ age at birth of caselreferent. There was no statistically significant difference in the mean age between fathers of cases and fathers of controls. , , Characteristics of mothers. Chronic illnesses (hypertension, heart disease, renal disease, epilepsy) were uncommon in mothers of cases and controls and no differ*ences were found. Diabetes mellitus, alcohol/drug abuse and malformations were not found in any mother. The occurrence of spontaneous abortions and stillbirths in prior pregnancies were similar in both groups. During the pregnancy/delivery, the civil status and presence of pelvic contraction did not differ between mothers of cases and controls. There was no difference between cases and controls in birth order and age of the mothers at birth of cases or controls. Of the cases, 45.5% were first born and among controls, 37.6% (OR= 1.35; p=0.25). Table 2. Events during the gestation of cases with FC (n= 10) and controls (n=213), (%). Odds ratio (OR) and p-values Frequency (Yo) Events during gestation
Cases
Controls
OR
P
Onset of hypertension Proteinuria Weight increase > 2 kglweek Maternal diabetes mellitus Colitis, proctitis, Morbus Crohn Hyperemesis Epileptic seizure Toxicosis Pre-eclampsia Eclampsia Toxicosis or pre-eclampsia Preeclampsia or eclampsia
13.6 7.3 0 6.4 2.7 2.7 0 9.1 2.7 0.9 11.8 3.6
7.5 0.9 0.5 2.8 0 0.5 0.5 6.6 0 0 6.6 0
1.90 8.04
0.13 0.01 0.74 0.32 0.07 0.23 0.73 0.58 0.07 0.74 0.17 0.02
2.00 5.94 1.40 1.88
Pre- and perinatal factors in febrile convulsions 22 1
Acta Paediatr Scand 80
Pregnancy. Table 2 shows the distribution of events that occurred during the gestation. Proteinuria occurred more often in mothers of cases. Pre-eclampsia or eclampsia were more common in mothers of cases, although both were rare events. There were no differences between groups regarding the occurrence of twin pregnancies, anemia, vaginal bleeding, placenta praevia, ablatio placentae, infections, maternal diabetes mellitus, epileptic seizures, surgery, diagnostic amniocentesis, drug consumption, alcohol abuse and smoking. Delivery characteristics. There were no differences between cases and controls with respect to factors occurring during delivery. The following factors were investigated: type of anesthesia, use of surgical or medical induction, Cesarean section, use of forceps or vacuum extraction, mode of presentation, meconium staining and obnoxious smell of amnion fluid, placental and umbilical abnormalities and duration of delivery. The fetal heart rate was monitored and related to uterine contractions by cardiotocogram in 56% of cases and 57% of controls. Abnormalities such as tachycardia > 160, bradycardia < 100 for more than 1 min, decreased variability and latehariable decelerations were equally common in cases and controls. Meconium staining of amnion fluid, another sign of prenatal asphyxia, were also equally distributed between groups. Gestational age and birthweight. When birth characteristics were investigated it was found that cases were more often born preterm (Table 3). Mean gestational age at birth was 38.6 weeks (SD=2.2) for cases and 39.2 weeks (SD= 1.8) for referents (Student’s t-test, p=O.OI). The mean birthweight of cases was 3.438 kg (SD=0.55) and of controls 3.562 kg (SD =0.60). The difference was not statistically significant (Student’s t-test: p=O.O6). Neonatal characteristics. Most children spent 5-7 days at the hospital. During this period there were no differences between groups in occurrence of respiratory disorders, heart disease, affections of the central nervous system and malformations. Laboratoryfindings. The mean gestational age of cases and controls with serum bilirubin > 200 pmol/l was lower than for cases and controls with normal bilirubin (cases: 36.7 vs. 39.1 weeks, p 41 complete weeks < 38 complete weeks < 37 complete weeks Child characteristics Birthweight < 2 500 g Small for gestational age Large for gestational age Apgar score < 6 at 1 min Apgar score < 6 at 5 min 15-918302
Cases
Controls
OR
p
1.8 19.1 13.6
1.4 10.8 4.7
1.29 1.94 3.19
0.82 0.06 0.01
8.2 1.8 2.7 6.4 0.9
4.2 0.9 7.0 2.3 0.9
1.96 1.89 0.36 2.84 1.05
0.25 0.88 0.16 0.13 0.57
222 L. Forsgren et al.
*
Acta Paediatr Scand 80
tional weeks and of the 20 controls with hyperbilirubinemia (>200 pmol/l), 7 (35%) were born before 37 completed gestational weeks. Thus, the more common occurrence of hyperbilirubinemia in cases is partly explained by a larger proportion of prematurity among cases compared with controls. Hence, when only the cases and referents born 3 37 completed gestational weeks were compared, no statistically significant difference was found (Table 4). Significantly more cases than controls had hyperbilirubinemia of such a degree that it warranted treatment (phototherapy or blood exchange transfusion). One child (case) had a serum bilirubin of 172 pmol/l but was treated with phototherapy because of profound prematurity (30 weeks). When the 1 1 children with a serum bilirubin > 300 pmol/l were compared, no difference between groups were found (odds ratio 3.55; p=0.07). There was no difference between groups in the occurrence of hypoglycemia and hypocalcemia. Complications combined. In order to compare the pre- and perinatal variables assessed by Heijbel et al. (3), occurrence of one or more of the following was cornpared between groups: maternal diabetes mellitus or essential hypertension, pre-eclampsia, vaginal bleedings, cesarean section, vacuum extraction, breech delivery, second twin, birthweight 342 pmol/l and congenital heart disease. At least one complication occurred in 49% of cases and 41 % of controls. Two or more complications occurred in 16% of cases and controls. The difference between groups was not statistically significant (OR= 1.37; 95 Yo confidence limits 0.86, 2.18). Two variables were included in the model (pt0.05)when stepwise logistic regression was applied on all variables that were statistically significant in the bivariate analysis or had been suggested to be of importance in the literature. These were gestational age < 37 complete weeks and other than normal mode of presentation at delivery.
DISCUSSION Wallace (12) found, in a hospital-based study, that mothers of children with FC more often suffered from chronic medical illnesses than mothers of controls and that mothers to males with FC were subfertile in an interval of 1-2 years preceding and following birth of the child with FC. No such difference was found in the Table 4. Hyperbilirubinemia, hypoglycemia and hypocalcemia of cases with FC and controls (%). Odds ratio (OR) and p-values Frequency (Yo) Variables
Cases
Controls
OR
p
Hyperbilirubinemia Hyperbilirubinemia and 2 37 weeks Hyperbilirubinemia and < 37 weeks" Treated hyperbilirubinemia Treated hyperbilirubinemiaand 3 37 weeks Treated hyperbilirubinemiaand
