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Biomedical subjects

V K Hiilesmaa

Publications and source records attributed to V K Hiilesmaa.

At least 19 recordsLinked to original sources

Oral poliovirus vaccination and pregnancy complications.

BACKGROUND: To determine whether the effect of live attenuated oral polio virus vaccine given to pregnant women increases pregnancy complications. METHODS: A study of women who had been vaccinated against poliovirus during a national vaccination campaign and who had delivered by cesarean section in three obstetrical hospitals in southern Finland. One thousand seven hundred and forty-seven vaccinated women (in three study cohorts), and their 2293 nonvaccinated controls (in two reference cohorts) were analyzed. Subjects are out of 22,000 deliveries evaluated earlier. RESULTS: Vaccinated sectioned women did not show an excess of pregnancy complications. The mean rate of cesarean sections was 18.4% in the study cohorts and 18.9% in the reference cohorts counted from the 22,000 deliveries. CONCLUSIONS: Oral live attenuated polio virus vaccine does not increase pregnancy complications and is considered a safe alternative for vaccinating pregnant women.

Adult

Objectively measured perinatal exposure to meperidine and benzodiazepines in Finland.

We measured concentrations of meperidine and benzodiazepines in the umbilical serum of all live neonates born in Finland during a single week. Of the neonates, 31.1% were exposed to meperidine or benzodiazepines or both. One hundred twenty-one mothers of the 261 neonates exposed to meperidine were not recorded in the Finnish Medical Birth Registry as having received analgesic drugs. Infants born to primiparous mothers were more likely to be exposed. The exposures were associated with the type of delivery: vacuum extraction with a high proportion of neonates exposed to meperidine and elective caesarean section with a high proportion of neonates exposed to benzodiazepines. The exposures were influenced by the method of obstetric analgesia: epidural blockade was associated with more frequent exposure to meperidine. No significant circadian variation in exposures was detected. Validation of birth registry data is imperative before they are used for pharmacoepidemiologic studies.

Adult

Oral polio vaccination during pregnancy: lack of impact on fetal development and perinatal outcome.

Prompted by a nascent epidemic of poliomyelitis in Finland, a mass vaccination program with live oral poliovirus vaccine (OPV) was implemented in February and March 1985. The final rate of coverage was approximately 94%. Pregnant women were included, and a cohort study was launched to evaluate any harmful effects of OPV on the developing embryo. All records of births to mothers who were pregnant during the period of vaccination and whose infants were delivered at the three major hospitals in the Helsinki area were reviewed. Within the study cohort, mothers were grouped into three categories according to their trimester of pregnancy during the program. In addition, two reference cohorts were evaluated; these cohorts consisted of infants delivered at the same hospitals during the second half of 1984 and of 1986, respectively. Each of the three categories in the study cohort included approximately 3,000 children, while each reference cohort included approximately 6,000 children. Data were analyzed on the rate of intrauterine growth and the prevalences of stillbirth, neonatal death, congenital malformation, premature birth, perinatal infection, and neurological aberration. No differences were documented among the study and reference cohorts or among the three categories within the study cohort. Thus, under the conditions described here, the inclusion of pregnant women in programs of mass vaccination with OPV appears to be safe.

Cohort Studies

Oral polio vaccination during pregnancy: no increase in the occurrence of congenital malformations.

To examine the possible association between maternal vaccination with oral polio-virus and congenital malformations of the child, use was made of a nationwide mass vaccination in Finland. During a restricted period in 1985, a vaccination with trivalent oral poliovirus was implemented with coverage of 94% of the population. The study population was chosen from three major hospitals in the Greater Helsinki Region in Finland which deliver over 95% of the children of their catchment area. One study and two reference cohorts were delineated; the former consisted of pregnancies that were in their first trimester during the vaccination period. The two reference cohorts included mothers from the same hospitals whose pregnancies were likewise in the first trimester during the corresponding time period in 1984 and 1986, i.e., 12 months before and after the study period. Each cohort consisted of approximately 3,000 mothers/children whose delivery and hospital records were manually perused by trained nurses. All the structural malformations reflecting an impaired organogenesis during the sensitive first trimester were monitored. A total of 209 (2.3%) such malformations were recorded and characterized. There were no differences between the study and reference cohorts (risk ratio = 0.7, 95% confidence interval 0.5-1.0). According to the authors' power estimate, an additional prevalence greater than 0.5% would have been detected. The authors conclude that administration of oral poliovirus vaccine during early pregnancy was not associated with an elevated risk of congenital malformations.

Cohort Studies

Randomized trial comparing first-trimester transcervical chorionic villus sampling and second-trimester amniocentesis.

A total of 800 patients were randomized at the 9th to 11th week of pregnancy either for transcervical chorionic villus sampling (CVS) on the day of trial entry or for amniocentesis (AC) at the 16th week. The indication for fetal karyotyping was maternal age in 94 per cent of the cases; the mean maternal age was 39.2 years. An adequate sample was obtained in 98.3 per cent of the cases in the CVS group and in all cases in the AC group. Retesting was indicated in 3.3 per cent of the CVS cases. An abnormal karyotype was found in 6.1 per cent of the CV samples and in 4.5 per cent of the amniotic fluid samples. There was one false-positive chromosome result in both groups. Twelve (3.1 per cent) miscarriages occurred by the 22nd week of pregnancy in the CVS group in pregnancies intended to continue. No difference was seen between the groups for total fetal loss rates. The number of surviving infants in the CVS group was 92.2 per cent and in the AC group 91.7 per cent (rate difference 0.5 per cent (95 per cent confidence interval -3.3 to 4.3)). In our study, both the diagnostic accuracy and the risk of fetal loss were equal in the CVS and AC groups.

Abortion, Spontaneous

Objectively measured tobacco exposure during pregnancy: neonatal effects and relation to maternal smoking.

OBJECTIVES: To measure quantitatively and objectively the maternal and fetal tobacco exposure during pregnancy and its neonatal effects. DESIGN: Tobacco exposure was assessed from maternal serum samples, obtained during the first half of pregnancy and from umbilical serum samples obtained at delivery, by measuring the concentration of nicotine metabolite, cotinine. Data on the respective pregnancies and neonates were collected from the Finnish Medical Birth Registry. SETTING: Finland. SUBJECTS: One thousand two hundred and thirty-seven pregnancies and newborns, representing all pregnancies resulting in a liveborn infant during one week in one country. MAIN OUTCOME MEASURES: Gestational age, birthweight and crown-heel length of newborns. RESULTS: Cotinine (> 6 micrograms/l) was detected in either maternal or umbilical serum in 300 pregnancies, and these mothers and newborns were classified as exposed. Important differences occurred between measured exposure and reported smoking behaviour. Of the exposed mothers, 38% were nonsmokers and 3.4% of the nonexposed mothers were smokers. Tobacco exposure was associated with shorter gestational age, reduced birthweight and shorter crown-heel length of the newborns. After correction for parity, gender, and gestational age, the exposed newborns were on average 188 g (95% confidence interval (CI) 123-253 g) lighter and 10 mm (95% CI 7-13 mm) shorter than the nonexposed newborns. One micrograms/ml of cotinine in maternal serum resulted in a mean decrease of 1.29 g (95% CI 0.55-2.02 g) in birthweight and in a mean decrease of 0.059 mm (95% CI 0.035-0.083 mm) in birth length. Maternal cotinine concentrations better explained the neonatal findings than the reported smoking habits. CONCLUSIONS: There is a quantitative dose and effect relation between tobacco exposure and a decrease in the gestational age at birth and size of the neonate. The smoking habit reported by mothers themselves is not an accurate measure of fetal tobacco exposure.

Adult

Pregnancy and birth in women with epilepsy.

The literature pertinent to obstetric aspects of the pregnancies in women with epilepsy is reviewed. The small risk (1%) of malformations of fetal central nervous system attributed to the use of carbamazepine or valproate during pregnancy should not discourage women who take these drugs from having children since these malformations can be reliably diagnosed (as well as excluded) during the 15th to 19th weeks of pregnancy with alpha-fetoprotein determinations and high-resolution ultrasound scans. Except for the 1.2- to 3-fold increase in perinatal mortality, the course of pregnancy and labor in women with epilepsy is usually uneventful. Most can have a normal vaginal delivery. Cesarean section is warranted only in a select minority of the difficult cases. Counseling, follow-up, and treatment of pregnant women with epilepsy should be provided at centers with the experience and resources to attend to the very specific problems that sometimes develop.

Abnormalities, Drug-Induced

Head circumference in children of epileptic mothers: contributions of drug exposure and genetic background.

Head circumference after the first year of life was investigated in 144 children of epileptic mothers ('study group'). Fifty-two children had been exposed to phenytoin monotherapy, 19 to carbamazepine monotherapy, 27 to drug combinations including barbiturates, 29 to other drug combinations, and 17 children had not been exposed to antiepileptic drugs (AEDs) during pregnancy. The prevalence of microcephaly (2.1%) was no higher than that in the general population. Head circumference was measured at 5.5 years in 121 of the study group children, in 105 control children, and in the majority of their parents (118 mothers and 89 fathers in the study group, and 103 mothers and 65 fathers in the control group). The sex-adjusted head circumferences of the children showed a significant variation according to exposure subgroup, with the barbiturate and carbamazepine monotherapy exposed children having the lowest mean values. This result is similar to our previous findings in the same children at birth and at 18 months of age. Paternal head circumference was also below average in the same subgroups. After further adjustment for parental head circumference, the significant variation between the subgroups of children disappeared, even though the barbiturate exposed children continued to have the lowest mean value. Genetic causes may thus contribute to the relatively small head circumference in some AED exposed children of epileptic mothers. However, a mild drug effect in the barbiturate and carbamazepine exposed children cannot be excluded.

Adult

Protein binding of antiepileptic drugs during pregnancy, labor, and puerperium.

Twenty-four epileptic women were followed-up during late pregnancy, labor, and early puerperium in order to detect possible alterations in serum protein binding of antiepileptic drugs (AEDs). The total and free concentrations of carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA) in maternal serum were measured. In addition, the concentrations of albumin, alpha 1-acid glycoprotein (AGP), and free fatty acids (FFA) were also measured. Total AED concentrations during labor were influenced by changes in drug dosages; total PHT increased during the first puerperal weeks. During labor the free fraction of CBZ remained stable, whereas PHT and particularly VPA free fractions increased. This phenomenon was parallel to the increase in FFA concentration; FFA concentrations decreased again during the first days postpartum. Albumin and AGP concentrations were low during pregnancy and labor, and increased after delivery. The total umbilical CBZ and PHT concentrations were not significantly different from maternal concentrations. The total VPA concentration in umbilical serum was significantly higher than that in maternal serum. The free fraction of CBZ was higher and that of PHT and VPA lower in umbilical than in maternal serum at delivery. Umbilical cord serum had a higher albumin but a lower AGP and FFA concentration than maternal serum. The changes in PHT and particularly VPA free fraction associated with changes in FFA concentration should be considered when assessing the total concentration of these drugs in maternal and umbilical serum.

Adult

Effect of pregnancy on the electroencephalogram of epileptic women.

The electroencephalograms (EEGs) of epileptic women in late pregnancy were compared with their EEGs outside pregnancy and the puerperium. The number of epileptic interictal discharges was not modified by pregnancy. Visual scoring and frequency analysis demonstrated a slight increase in the alpha band during pregnancy. No correlations were found between the EEG findings and changes in seizure frequency.

Adult

Serum phenytoin during pregnancy, labor and puerperium.

111 pregnancies of epileptic women on phenytoin therapy were observed in a prospective study. Maternal serum phenytoin concentrations were measured monthly or bi-weekly during pregnancy, labor and puerperium. The concentration decreased towards the end of pregnancy and was lowest at delivery. In 48% of the patients the drug dosage had to be increased to combat the increased seizure frequency.

Adult

Obstetric outcome in women with epilepsy.

A comparison of 150 pregnancies in women with epilepsy and 150 pregnancies in matched nonepileptic control women showed similar rates of pregnancy-induced hypertension, albuminuria, premature contractions, premature labor, and bleeding in pregnancy. Duration of labor, blood loss at delivery, cesarean section rates, and vacuum extraction rates were also similar among epileptic and control groups. There were five perinatal deaths in the epileptic group and two in the control group. A fetal heart rate tracing during a maternal grand mal seizure showed bradycardia, reduced short-term and long-term variability, and late decelerations suggesting asphyxia. It is concluded that grand mal seizures during pregnancy should be avoided by the use of antiepileptic drugs. Women with epilepsy require antenatal neurological and obstetric follow-up during pregnancy.

Anticonvulsants

Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome.

Serum folate concentrations, blood counts, and antiepileptic drug concentrations were measured during 133 pregnancies of 125 women with epilepsy. There was an inverse correlation between serum folate concentrations and concentrations of phenytoin and phenobarbitone. The number of epileptic seizures during pregnancy showed no association with serum folate concentrations. No cases of maternal tissue folate deficiency or fetal damage attributable to low maternal serum folate were observed. Maternal serum folate concentrations for infants with structural birth defects, "fetal hydantoin syndrome," or perinatal death were similar to those for healthy babies. A low dose (100 to 1000 micrograms daily) of folate supplement appeared sufficient for pregnant women with epilepsy despite the antifolic action of antiepileptic medication. Monitoring folate concentrations in pregnant women with high serum concentrations of phenytoin or phenobarbitone is recommended.

Carbamazepine

Evaluation of placental function in women on antiepileptic drugs.

Placental function in the presence of antiepileptic drugs was assessed in 144 unselected late pregnancies of women with epilepsy. The most common drugs of the mothers were phenytoin (104 pregnancies), carbamazepine (42) and phenobarbitone (26). 144 control parturients matched for maternal age, parity, fetal sex and social class were also studied. No significant associations between the types or the serum concentrations of the mother's antiepileptic drugs and her serum HPL, 24-hour total urinary estriol excretion, placental weight or her child's birth weight were observed. However, since the serum levels of antiepileptic drugs were usually within or below the therapeutic ranges the study does not exclude the possibility that very high drug concentrations might have some effects. The incidences of common pregnancy complications did not differ between epileptics and controls. Serum HPL and urinary estriol values in epileptic women agreed well with the references for normal. It is concluded that the long-term use of antiepileptic drugs during pregnancy has no clinically important effects on placental function or on its biochemical tests in spite of the enzyme induction properties of these drugs. Values of serum HPL and 24-hour total urinary estriol excretion can thus be interpreted in the usual manner in women who are on antiepileptic medication.

Adult