Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin-thromboxane balance in mother and newborn.

OBJECTIVE: To study the effect of daily treatment with 50 mg of aspirin (ASA) on the hypertensive pregnancy complications and on the production prostacyclin (PGI2) and thromboxane A2 (TxA2) in high risk pregnant women and their infants. DESIGN: Placebo controlled prospective study. SETTING: Departments of Obstetrics and Gynaecology, University of Helsinki, University of Oulu and Central Hospital of Middle Finland, Finland. SUBJECTS: Two hundred and eight pregnant women with pre-existing hypertension or a history of severe preeclampsia in their previous pregnancy. Prostanoids were studied in a subgroup of 18 women. INTERVENTIONS: The women were randomised to receive ASA (50 mg/day, n = 103) or placebo (n = 105) from the mean of 15 weeks gestational age to delivery. The exacerbation of pre-existing hypertension or the appearance of hypertension in previously normotensive women, the appearance of proteinuria and fetal growth were the main end points, but some other clinical characteristics were also recorded. Urinary excretion of PGI2 and TxA2 metabolites by mothers and infants and their production in umbilical arteries in vitro were also studied. RESULTS: Two women (one in both groups) had miscarriages, and one pregnancy was terminated for fetal anencephaly (ASA group). In addition, seven women discontinued the treatment due to urticaria (two women in ASA group), increased activity of aspartate amino transferase in serum (one woman in both groups), or increased bleeding time (one woman in ASA group, two women in placebo group), and one woman in the placebo group was lost from follow-up. Thus the end points could be assessed in 97 women taking ASA and 100 women taking placebo. ASA did not diminish the rate of the rise of blood pressure without (12 vs 14, respectively) or with proteinuria (9 vs 11), but fetal haemodynamic disturbances as assessed by Doppler equipment (1/44 vs 6/45 women studied, P = 0.05) and need for treatment in neonatal intensive care unit (10 vs 21, P = 0.04) were more rare in ASA group. ASA tended to increase the birthweight of the newborn (3348 +/- 707 g vs 3170 +/- 665 g, mean +/- SD, P = 0.07), but two perinatal deaths occurred in ASA group. ASA prolonged the bleeding time of the mother (435 s, 210-998 s (geometric mean, range) vs 349 s, 210-690 s, P = 0.02), but caused no extra blood loss during delivery, nor affected neonatal hemostasis. In a subgroup of mothers (ASA, n = 10; placebo, n = 8), ASA inhibited more than 90% of platelet TxA2-production, and caused a 65 to 80% decrease in the urinary excretion of TxA2 metabolites, but no decrease in the urinary excretion of PGI2 metabolites. CONCLUSIONS: ASA did not prevent the rise of maternal hypertension, but improved fetal haemodynamic performance and reduced the need of intensive neonatal care. It inhibited strongly maternal thromboxane A2 but not PGI2 production and thus shifted the balance between PGI2/TxA2 to the dominance of the vasodilatory, anti-aggregatory side.

Obstetric shoulder injury. Associated risk factors, prediction and prognosis.

A prospective case-control study was made to estimate the incidence of clavicular fracture and brachial plexus palsy, to find out possible risk factors during pregnancy and labor associated with these injuries, and to ascertain the prognosis of injured infants. Clavicular fracture occurred in 165 (3.2%) and brachial plexus palsy in 10 (0.2%) of the 5082 infants born during the study period. From maternal characteristics the Body Mass Index (kg/m2) and pregnancy weight gain were significantly greater in the cases than in the controls. Symphysis-to-fundus height was, on average, higher in the case group. There were no more instrumental vaginal deliveries in cases than in controls. The shoulder injured infants were in every way bigger, but only in 30% of the cases macrosomic (birthweight over the 90th percentile), and they were more often males than in the controls. The prediction of shoulder injury by ultrasound was not successful in our study. The prognosis of injured infants was good, all children except one recovered soon after birth.

Labour induction policy in hospitals of different levels of specialisation.

OBJECTIVE: To examine indications for the induction of labour and variations in the current policy of induction at different levels of obstetric specialisation and to compare the outcome of induced and spontaneous labour. DESIGN: A prospective 1 year birth cohort. SETTING: Maternity hospitals in the two northernmost administrative provinces of Finland, including one university hospital and three central hospitals, three local hospitals and five health centres. SUBJECTS: Eight thousand six hundred and six singleton pregnancies, including 1679 with induced labour. MAIN OUTCOME MEASURE: Data collection on age, parity, social factors and education at antenatal clinic. Data on labour collected from the hospital records after delivery. RESULTS: Labour was induced significantly more often at units of the lowest level of specialisation, the health centres (29.4%) than at the local hospitals (23.6%, P < 0.003) or in the most specialised central hospitals (17.7%, P < 0.0001). Cases of induced labour accumulated on working days. Indicative reasons, such as maternal or fetal conditions, comprised 45.0% of the indications for induction, the most common causes being elective reasons, e.g. timing of labour (51.3%). The risk of elective induction was 2.6 times greater at the primary care level than at the central hospitals (95% confidence limit, CL 2.0-3.2). The corresponding risk ratio for local hospitals was 1.8 (CL 1.5-2.1). The risk of caesarean section was 1.5 times greater in the elective induction group than in the spontaneous group (CL 1.1-1.9) and 2.9 times greater in the indicative induction group. The most common indication for caesarean section was dysfunctional, arrested labour, causes such as fetal asphyxia or antenatal haemorrhage were not seen in excess. CONCLUSION: The practice of induction of labour are not consistent in different hospitals. The opinions of individual practitioners and staff routines influence the induction policy nearly as much as do medical reasons. Despite the safety of induction, a liberal induction policy leads to an increase in operative deliveries creating potential risks for the mother and child and greater expense.

Perinatal outcome of pregnancies complicated by vaginal bleeding.

OBJECTIVE: To examine the effect of first and/or second trimester vaginal bleeding on pregnancy outcome. DESIGN: A prospective one-year birth cohort. SETTING: Two northernmost administrative districts of Finland. PATIENTS: 8718 singleton pregnancies, of whom 807 (9.3%) reported bleeding during the first (601) and/or second trimester (206); light bleeding in 595 cases and heavy bleeding in 212. The remaining 7911 women served as a reference group. MAIN OUTCOME MEASURES: Low birth weight rate (LBW), preterm birth rate, congenital malformations and perinatal mortality rate. RESULTS: Bleeding was most frequent in women of more advanced age (> or = 35 years old), with previous miscarriages, with infertility problems or using an IUCD prior to the pregnancy. Parity, smoking and social status were not associated with bleeding. Caesarean section rate and placental complications during the third trimester and at delivery were more common among the bleeders than in the reference group. The LBW rate was three-fold among the bleeders and the preterm birth rate two-fold. The risk (OR) of a LBW infant among second trimester bleeders was 4.1 (95% CI 2.6-6.4), that of preterm birth 2.9 (95% CI 1.9-4.6), and that of congenital malformations 2.9 (95% CI 1.7-4.7). No association existed between bleeding and perinatal mortality. CONCLUSIONS: Bleeding during the second trimester indicates a poor pregnancy outcome and an increased risk of LBW, and preterm birth and/or congenital malformation.

Occurrence of antinuclear antibodies in an unselected pregnancy population.

The occurrence of antinuclear antibodies (ANA) in an unselected population of pregnant women was studied by an indirect immunofluorescence method. Six women out of 116 were ANA-positive (5.2%), 2 of them having a moderately high titre (1:160 and 1:320) and 1 complement-fixing ANA. The antigenic specificity of ANA was anti-single-stranded DNA in 2 cases and RNAase-sensitive anti-extractable nuclear antigen in 1 case. Two of the ANA-positive women had pre-eclampsia laevis and 1 had a premature delivery. None of the infants of the ANA-positive women had symptoms of connective tissue disease. The occurrence of ANA among pregnant women was not significantly higher than among 70 non-pregnant female control subjects (7.1%).

Monitoring of smooth muscle antibodies in hypertensive complications during pregnancy.

Smooth muscle antibodies (SMA) were monitored in terms of titer, immunoglobulin class and staining pattern by indirect immunofluorescence assay during the pregnancies of 32 women with pregnancy induced hypertension (PIH), 21 with essential hypertension (EH), and 43 with a normal pregnancy. The mean SMA titer was higher both in PIH and EH than in normal pregnancy. SMA were mainly of the IgG class and gave a "vessel wall" staining pattern in immunofluorescence. The tendency for the mean SMA titer to increase was observed in PIH, whereas a falling tendency was found in EH and normal pregnancy. These tendencies suggest that hypertension, the duration of which has been shorter in PIH, induces SMA production. The observed staining pattern suggests the same kind of non-actin specificity for SMA as in our previous study of complications in early pregnancy.

No effect of experimental noise exposure on human pregnancy.

The effect of experimental noise exposure (15 minutes of 90-dB white noise via headphones) was examined on systolic, diastolic, and mean arterial pressures; heart rate; and stress hormones (ACTH, cortisol, prolactin, epinephrine, and norepinephrine) in normotensive and hypertensive pregnant women. No significant effects induced by noise exposure could be registered in these variables. Fetal and uterine blood circulation was also examined with a duplex pulsed Doppler system. No changes were seen on the fetal side as measured from the descending aorta in blood flow velocity (cm/second) or pulsatility or resistance indexes in either normotensive or hypertensive pregnancy. The only change observed was an increase in fetal heart rate in normotensive pregnancy. However, this increase could not be confirmed by cardiotocographic registration and is not clinically important. Uterine blood circulation was recorded from the proximal uterine artery on the placental side, and no effect of exposure was seen on pulsatility or resistance indexes.

Immediate correction of congenital nasal deformities; follow-up of 8 years.

A total of 4724 newborns was screened for congenital nasal deformities. Altogether 91 (1.9%) pathological, screening-positive cases were found. Because of refusal to participate, 3 pathological cases were lost leaving 88 cases. The first 55 screening positive newborns were left without treatment while an attempt was made by an otolaryngologist to correct the remaining 33 cases within a week from delivery. Eighty-two newborns of those who passed the screening tests were analyzed as a control group. In 1987, at the age of 8 years the case and control children were interviewed by mailed questionnaire and invited to be re-examined by an ENT-surgeon. Forty-seven of the not corrected, 21 of the corrected cases and 61 controls came to the re-examination. The luxated septal cauda tended to be straight both spontaneously as well as after active treatment. The few mid-septal pathologies (vomerine junction) in the corrected group were resistant to the treatment attempted. The mid-septal deformities found in the follow-up were connected with frequent antibiotic prescriptions but not respiratory infections. No increase in frequency of otitis media or sinusitis was noticed. The immediate treatment of nasal deformities did not significantly affect the clinical status of the nose at the follow-up. Thus the benefit of immediate treatment on nasal deformities in newborns and screening to find them remains questionable.

Is a child's history of acute otitis media and respiratory infection already determined in the antenatal and perinatal period?

A random sample of 2512 children were followed up from fetal period to the age of two years and the relation of various antenatal and perinatal factors to acute respiratory infection, wheezy bronchitis and otitis media was studied. A model containing the relationships between the variables was used as a basis for the analysis and the powerful confounding effects of postnatal factors were standardized. Acute otitis media with effusion (AOME) demonstrated by myringotomy was analyzed as a specific subgroup of acute otitis media (AOM). Low birth weight (less than or equal to 2500 g) and prematurity (birth before the 37th gestational week) did not influence either AOM or AOME. The odds ratio for low birth weight infants becoming 'otitis-prone' (greater than or equal to 3 episodes of AOME) was 1.5 (0.9-2.1, P greater than 0.1). The various neonatal ventilation therapies were not associated with either AOM or AOME, but intermittent positive pressure ventilation, low birth weight and prematurity were distinctly related to wheezy bronchitis. The odds ratio regarding intermittent positive pressure ventilation was 2.0 (1.0-3.0, P less than 0.05) and that regarding low birth weight 1.7 (1.0-2.3, P less than 0.05). Boys had a slightly increased risk with respect to all the infective parameters. Birth order was closely correlated with the infective parameters, but much of this correlation was due to the postnatal effect of siblings. Altogether the antenatal and perinatal factors had only a slight effect on the infective parameters studied.

Changes in prognosis of twin births over 20 years.

The study is based on two birth cohorts from the years 1966 and 1985-1986. Perinatal mortality of twins has fallen over 20 years from 9.2% to 3.1%. Improvement is particularly remarkable in neonatal mortality (less than 28 days) of preterm (less than 34 gestational weeks) twins, from 47.4% to 8.6%, whereas the incidence of stillbirths has not fallen greatly. The proportion of preterm births has not fallen significantly, 48.4% vs. 38.1%. Many factors, considered favourable to the course and outcome of pregnancy have improved simultaneously: women are taller, less overweight, and more educated; pregnancies are wanted and sick and maternity leave provisions have improved. The follow-up of twin pregnancies and deliveries has been centralized and is more effective. In particular, neonatal care is also better than 20 years ago. The prognosis of twins has improved in parallel with the singletons, but the perinatal mortality is still approximately four time and the incidence of prematurity ten times more than in singletons.

The grand multipara--still an obstetrical challenge?

To study whether grand multiparity (parity of 6 or more) still carries risk, we studied two birth cohorts in northern Finland: the first comprised 12,231 births to 12,068 mothers in 1966 and the second comprised 9478 births to 9362 mothers in 1985/86. The percentage of grand multipara decreased from 7.7 to 4.0. The grand multipara made fewer antenatal visits than the others. The proportion of grand multipara referred to maternity outpatient clinics of hospitals was smaller, but the mean number of visits was higher than of lower parity women. The mean number of admissions to hospital was similar in both groups but grand multipara stayed longer in hospital, smoked less (4.3% vs. 22.7%) and had a higher incidence of essential hypertension than women of lower parity. The grand multipara had fewer caesarean sections (7.5% vs. 14.1%) and vacuum extractions (0.5% vs. 5.1%) but more inductions of labour (33.1% vs. 23.5%) than mothers of lower parity. The number of low birth weight (LBW) infants (less than 2500 grams), stillbirths and neonatal deaths (before 28 days) was significantly lower in 1985/86 than in 1966 in women of lower parity but there was no such change in grand multipara. However, the percentage of LBW infants was smaller among grand multipara than among women of lower parity in both cohorts (2.7% vs. 4.1%, NS). The stillbirth plus neonatal death rate in grand multipara was higher than in women of lower parity (1.9% vs. 0.9%, P less than 0.05) partly because of a higher incidence of major congenital anomalies.

Occupational and socio-medical factors in preterm birth.

Two hundred eighty-four women who had preterm deliveries and matched controls who had full-term deliveries were analyzed using a conditional logistic regression model to assess the effects of employment and socio-medical factors on preterm birth. In the analysis, employment outside the home, in general, turned out not to be a significant risk factor for preterm birth. Of the social factors, unmarried status (odds ratio 2.0) and current smoking (odds ratio 2.4) were associated with preterm birth, as were medical factors such as hypertension (odds ratio 7.3), intrauterine growth retardation (odds ratio 3.9), and fetal malformations (odds ratio 5.2).

Maturation of immunoglobulin G avidity after rubella vaccination studied by an enzyme linked immunosorbent assay (avidity-ELISA) and by haemolysis typing.

Two tests were introduced recently for assessment of the avidity of rubella immunoglobulin antibodies. In the quantitative test--avidity-enzyme linked immunosorbent assay (ELISA)--IgG antibodies obtained from individuals shortly after primary infection with rubella virus are distinguished from those with past immunity by their antigen-elution characteristics. This method uses agents that disrupt hydrophobic bonds in proteins [Kamoun PP (1988): Denaturation of globular proteins by urea: Breakdown of hydrophobic bonds? Trends in Biological Sciences 13:424-425.]. In the semiquantitative, presumptive test--haemolysis typing--the low-avidity rubella-IgG antibodies are distinguished from the high-avidity antibodies by the quality of their haemolytic zones in a radial haemolysis test. In the present study, both tests were applied to sera taken before and after vaccination with two different strains (Cendehill or RA 27/3) of live attenuated rubella virus. It was found that after vaccination of previously nonimmune subjects, IgG synthesized during the first 2 months had a very low avidity; IgG avidity increased dramatically during the subsequent 4 months and less markedly between 6 and 12 months after vaccination. On the contrary, the initially high IgG avidity of previous immune vaccinees remained at an elevated level postvaccination. These results provide a basis for identification of recent primary rubella virus infections, or vaccination reactions, by the avidity of specific IgG and also for their separation from rubella reinfections.

Occupational noise exposure during pregnancy: a case control study.

The possible effects of occupational noise on human pregnancy were examined in a case-control study. The case groups consisted of 284 women with premature deliveries and of 299 women with full-term, low birth weight infants (below the 25th centile), each case having a matched pair. The whole material, all cases and controls included, comprised 1166 women. The percentage of employment in the whole material was 77.8; there were no differences between the case women and their controls. Rather few women (N = 26; 3.5%) reported occupational noise (greater than or equal to 81 dB; Leq(A)8h) during their pregnancies and our study revealed no significant difference between the cases (N = 14) and the controls (N = 12) with regard to noise exposure. Because of the small number of exposed women conclusions have to be drawn carefully. Nevertheless, noise cannot be regarded as a major risk for prematurity or low birth weight of human newborns in Finnish society. The women with reported noise exposure had significantly more inconvenience at work than other working women. They also had significantly more numerous and longer sick leaves than other working women.

Pharmacokinetics of clonidine during pregnancy and nursing.

Pharmacokinetics of clonidine were examined in ten women during pregnancy, in nine during nursing, and in the newborns of these women. Clonidine crosses the placenta easily, and its concentrations were equal in maternal serum and umbilical cord serum. Amniotic fluid concentrations were up to four times that found in serum. Clonidine concentrations in milk were roughly twice that in maternal serum; in the serum of the newborns the concentrations were about half those of the mothers. All concentrations corresponded well to the doses of the drug. The neurologic examinations and assessments of serum electrolytes and blood glucose showed results parallel with those of newborns of nontreated mothers.

Maternal residual beta-cell function and the outcome of diabetic pregnancy.

Preservation of own insulin production (residual pancreatic beta-cell function) has been shown to have a beneficial effect on glycemic control in insulin-dependent diabetic subjects, and its total lack has been suggested to be an independent risk factor during diabetic pregnancy. We studied the influence of residual beta-cell activity on the glucose control and the outcome of pregnancy in 29 diabetic women by sequentially measuring gestational postprandial plasma C-peptide (CPR) levels, diurnal blood glucose curves and blood glycosylated hemoglobin (Hb A1c) and by analyzing the morbidity and mortality of the offsprings. The 9 diabetics with moderate own insulin secretion (CPR levels over 1.0 microgram/l, White classes B and C, later referred to as group I) had significantly better glucose control than the remaining 20 subjects with lower CPR values (White classes C, D and NF, later referred to as group II) (figure 1, table I). There were two intrauterine deaths, both in group II. These deaths (one caused by multiple congenital contracture syndrome and the other by severe intrauterine growth retardation without any evident cause) could not be straightly connected with diabetes. Respiratory distress syndrome was seen in group II only. There was no other significant difference in the neonatal morbidity between the two groups (table II). All mothers of RDS infants were in White class NF where the birthweight was also smaller than in classes B and C. These were the only differences in neonatal morbidity between the White classes (table III). In conclusion, moderate residual beta-cell function seemed to be clinically important in maintaining strict glucose control during gestation.(ABSTRACT TRUNCATED AT 250 WORDS)