Increased maternal mortality in The Netherlands from group A streptococcal infections.

OBJECTIVE: To assess genital tract sepsis-related maternal mortality in The Netherlands during 1983-1992. STUDY DESIGN: A nationwide Confidential Enquiry into the causes of maternal death. RESULTS: Genital tract sepsis-related maternal mortality during 1983-1987 was 0.11 per 100,000 live births (1/893,998) and 0.93 per 100,000 live births (9/968,990) during 1988-1992. The relative risk of dying due to sepsis in the second 5-year period as compared to the first period was 10.1 (1/72 versus 9/72 maternal deaths; 95% CI 1.3-82.3; P < 0.01). CONCLUSIONS: Also in The Netherlands an increase of death due to genital tract sepsis has been observed since the 1980s.

The disappearance of fetal and donor red blood cells in alloimmunised pregnancies: a reappraisal.

OBJECTIVE: To determine the proportional reduction per day in the number of fetal and donor red blood cells from the fetal circulation after intrauterine intravascular transfusions. DESIGN: A retrospective study of 302 transfusions in 101 fetuses. SETTING: The Department of Obstetrics and Gynaecology of the University Medical Centre Leiden, The Netherlands. METHODS: We measured the haematocrit in fetal samples both before and after repeated intravascular intrauterine transfusion in fetuses with alloimmune disease. The percentage of fetal erythrocytes was determined in Kleihauer-Betke stained smears. The decline of fetal, donor and mixed red blood cells was calculated by dividing the proportional decrease of the haematocrit values of the number of days between transfusions, also after correction for changes in fetoplacental volumes. Results (given as mean [SD]) are derived from the proportional changes of haematocrit per day. RESULTS: The interval between the first and second transfusion (15.5 days [SD 5.2]) was shorter than between subsequent transfusions (means ranging from 21.4 to 21.9 days; P < or = 0.0001). The decline per day of mixed, and of donor red blood cells, calculated without corrections for volume changes did not differ from those corrected for volume changes resulting from the transfusion and from fetal growth (correction factor 1.1 [SD 0.4]). Since the coefficient of variance is smaller for the uncorrected decline values, this type of calculation is preferable for clinical purposes. The disappearance of fetal erythrocytes after the first transfusion (6.1%/day [SD 2.9]) was faster than that of mixed fetal and donor red blood cells (3.2%/day [SD 1.2]; P < 0.0001) and of donor cells alone (1.4%/day [SD 1.6]; P < 0.0001). The decline of the mixed red blood cell population became the same as that of the donor cells (2.2%/day [SD 0.8]) after the second transfusion. This decline of donor cells was higher than after the first transfusion (1.4%/day [SD 1.6]; P < 0.05). After the first transfusion the fetal erythrocytes disappeared faster after transplacental puncture of the umbilical cord (6.6%/day [SD 2.8]) than after transamniotic punctures (5.4%/day [SD 2.7]; P = 0.05). The mixed red blood cell also decreased faster (3.5%/day [SD 1.3] versus 2.8%/day [SD 0.9]; P < 0.01). CONCLUSION: The fast disappearance of fetal erythrocytes, especially after transplacental punctures, shows that the interval between the first and second transfusion needs to be shorter than that for intervals between subsequent transfusions. The number of donor erythrocytes declines by approximately 2% per day.

Underreporting of maternal mortality in The Netherlands.

OBJECTIVE: To establish the actual number of maternal deaths in The Netherlands by determining the degree of underreporting. METHODS: We conducted a nationwide, retrospective cross-check of the three available maternal mortality registration systems and issued a questionnaire to senior obstetricians in all hospitals during the years 1983-1992. RESULTS: The officially reported maternal mortality rate during the study period was 7.1 per 100,000 live births (133 maternal deaths per 1,862,985 live births). After completion of the study, our data indicate that the rate should be at least 9.7 per 100,000 live births (180 maternal deaths). Early pregnancy and indirect deaths were more likely to be underreported than direct deaths during labor and the puerperium. Failure to register the recent pregnancy on the death certificate was a frequent problem. Misclassification was particularly evident for cerebrovascular disorders, cardiovascular disorders, and eclampsia. CONCLUSION: The level of underreporting of maternal mortality in The Netherlands was estimated at 26%. The pregnancy status of women should be registered on death certificates. Officially reported maternal mortality rates are unreliable and international comparisons using these data thus are less meaningful.

Maternal mortality after cesarean section in The Netherlands.

BACKGROUND: To assess cesarean section-related maternal mortality in The Netherlands during 1983-1992. METHODS: A nationwide confidential enquiry into the causes of maternal death. RESULTS: The risk of dying after vaginal birth was 0.04 per 1000 vaginal births (65/1.763.999) compared to 0.53 per 1000 cesarean births (57/108.587). The direct risk of dying from cesarean section was 0.13 per 1000 operations (14/108.587). In some women cesarean section did not initiate, but contributed to, the train of events leading to death. Adding this associated risk to the direct risk gives a fatality rate of 0.28 per 1000 cesarean births (30/108.587). CONCLUSIONS: Although cesarean section is a relatively safe procedure nowadays, birth by cesarean section in The Netherlands is seven times more hazardous than vaginal birth. Keeping the cesarean birth rate as low as possible is therefore in the interest of women of reproductive age.

Follow-up of children born with an umbilical arterial blood pH < 7.

OBJECTIVE: We performed neurodevelopmental assessment in children born with an umbilical artery pH < 7. STUDY DESIGN: All infants born with an umbilical artery pH < 7 from a 19-month period were retrieved from the obstetric database. Obstetric, neonatal, and pediatric records were reviewed. At an age of 1 to 3 years, children were visited at home for semi-structured questioning of the mother and a Denver Developmental Screening Test of the child. RESULTS: During the study period 1614 umbilical artery pH measurements were entered in the database. Thirty (1.9%) were < 7. From this group 23 infants were admitted to the neonatal intensive care unit, and 8 of them required intubation. Twenty-eight children survived the neonatal period. Three children experienced an episode of mild hypertonia. One child had a mild motor developmental delay. CONCLUSION: Babies born with an umbilical artery pH < 7 are at greater risk to experience considerable short-term morbidity. Those who leave the neonatal intensive care unit without major problems have good outcomes, and pessimism in counseling their parents in unwarranted.

Follow-up of pregnancies, infants, and families after multifetal pregnancy reduction.

OBJECTIVE: To evaluate the course of multifetal pregnancies and also the long-term pediatric and psychosocial follow-up of surviving offspring and their parents after selective reduction. DESIGN: Follow-up study. SETTING: University hospital and subject's homes. PATIENTS: Twenty-one couples with high-order multiple pregnancies resulting from infertility treatment were referred from all over the Netherlands. A total of 36 infants (15 twins and 2 triplets) were included in the follow-up. INTERVENTION: Pregnancy reduction by transabdominal approach at a median of 11 (9 to 13) weeks gestation. One assessment took place between the age of 9 months and 6 years after delivery. MAIN OUTCOME MEASURES: Pregnancy outcome, health of the infants, and psychosocial impact upon their parents after infertility treatment and the multifetal pregnancy reduction. RESULTS: Abortion within 4 weeks after pregnancy reduction did not occur in this series. Six infants (13.7%) died perinatally. Two infants (4.4%) died at the ages of 12 days and 3 months, respectively. Early preterm delivery was the cause of death in all cases. The development of the infants was appropriate to gestational age and birth weight. At follow-up, 14 couples disclosed at the time they were unaware of the risks and the consequences of infertility treatment. Nine couples indicated they had feelings of guilt after pregnancy reduction. These feelings, however, were not disclosed at the time of the interviews, during which none of the families showed either regret or distress about their decision. Two couples only occasionally experienced some grief and mourning reactions for the reduced fetuses. CONCLUSIONS: Pregnancy reduction is an acceptable option in the case of excessive multifetal conceptions after infertility treatment regimes. There are no adverse effects on either the infants and their families provided that the procedure is carefully planned and performed and the couples are given full support both before and after the procedure.

The use of an episiotomy in relation to the professional education of the delivery attendant.

In a group of 1272 primiparous women, who delivered spontaneously at the University Hospital of Leiden between 1 January 1988 and 31 December 1991, the relationship between the use of an episiotomy and the professional training of the delivery attendant has been studied, using multiple logistic regression (a random effects model to allow for patient-within-physician effects). The following factors were taken into account: birthweight, duration of the second stage of labour, supposed fetal distress, age and race of the mother, gestational age, duration of pregnancy and the year of the delivery. Based on the logistic regression model it is estimated that registrars and gynaecologists are 2.5 and 3.4 times, respectively, more likely than midwives to perform an episiotomy.

No beneficial effect of low-dose fetal intravenous gammaglobulin administration in combination with intravascular transfusions in severe Rh D haemolytic disease.

Recent observations have shown that treatment with high-dose intravenous gammaglobulin (IVIgG) given to the mother may improve fetal outcome in cases of severe Rh D alloimmunization. Unfortunately, the costs of this new method of treatment are too high for routine use. Therefore, we decided to apply this treatment to the fetus and to investigate whether the effect of IVIgG might be attributable to blockade of the fetal mononuclear phagocyte system. We have performed a randomized study in which 20 fetuses with severe Rh D-haemolytic disease (HDN) were treated with intrauterine intravascular red cell transfusions (IUT). In 10 of these 20 cases transfusions were followed by administration to the fetus of low-dose IVIgG (85.7 +/- 11.6 mg/kg by ultrasound-estimated fetal weight because of fetal vascular volume considerations). We compared the number of IUTs, postnatal exchange transfusions, haematocrit (Ht) and haemoglobulin (Hb) values before and after transfusion (s) needed by the newborns of the two groups. No significant differences in the transfusion requirements of the fetuses and in the clinical outcome could be demonstrated. However, the 95% confidence interval for the difference in the improvement of cord blood Ht was too wide for any conclusions. The 95% confidence interval for the difference in the improvement of Hb levels suggests that any clinically relevant advantage of IVIgG on Hb is unlikely.

Breech delivery in very preterm and very low birthweight infants in The Netherlands.

OBJECTIVE: To study the relation between various perinatal factors and the sequelae of very preterm birth, applying logistic regression analysis. DESIGN: In a nationwide collaborative study in the Netherlands, perinatal and follow up data were collected on 899 liveborn singleton nonmalformed infants with gestational age less than 32 weeks or birthweight less than 1500 g born in 1983. MAIN OUTCOME MEASURES: Neonatal mortality rate and total handicap rates (minor and major) in surviving children at two years and five years of age. RESULTS: Comparing breech with vertex presentation, the odds ratio for neonatal mortality (adjusted for duration of pregnancy, birthweight, maternal hypertension and prolonged rupture of membranes) is 1.6 (P < 0.05). Comparing abdominal versus vaginal delivery, the odds ratio indicates equal risks. When breech and vertex presentation are analysed separately it appears that breech presenting infants have a significantly lower mortality risk when born by caesarean section compared with vaginal delivery. However, comparing abdominal versus vaginal delivery in breech presentation, the odds ratio for handicap at five years (0.9) is not significantly different from 1. CONCLUSION: The data presented suggest a reduced neonatal mortality rate in breech presenting infants born by caesarean section but because of the observational design of the study the statistical analysis described only identifies a possible trend and cannot prove the issue.

Evidence for the protective effect of maternal FcR-blocking IgG alloantibodies HLA-DR in Rh D-haemolytic disease of the newborn.

In cases of Rh D alloimmunization, strong results in the antibody-dependent cell-mediated cytotoxicity (ADCC) assay (> 80% lysis as compared to that of the standard anti-D serum) are indicative of severe hemolytic disease to occur in the newborn (HDN). However, discrepant cases were found in which the maternal anti-D gave strong ADCC results and the newborns had no or only mild hemolysis. In the majority of these cases the mother had produced monocyte-reactive IgG alloantibodies, mostly with HLA-DR specificity. Such antibodies may be capable of blocking FcR-mediated functions of the fetal MPS, and it has been postulated that they inhibit destruction of anti-D-sensitized red cells. We here describe 2 families in which such discrepancies were noticed. In 1 family, in spite of ADCC results of > 80%, the Rh D-positive second child was born without signs of hemolysis. However, the Rh D-positive third child suffered from very severe hemolytic disease. The mother had produced monocyte-reactive HLA-DR antibodies in the second pregnancy which, however, did not react with the cells of the third child. In the other family, the severely Rh D-alloimmunized mother had lost her fourth child because of intrauterine death due to HDN. The Rh D-positive fifth child was born with only mild HDN and only in this pregnancy had the mother produced such antibodies. These 2 case histories give further evidence that maternal monocyte-reactive alloantibodies, in both these cases directed against HLA-DR antigens, can protect the Rh D-positive child against hemolytic disease in case of severe Rh D alloimmunization.

Conservative management of placental abruption complicated by severe clotting disorders.

Placental abruption resulting in fetal death may seriously affect maternal health, especially when clotting disorders arise. The prevailing view is that the clotting system will only normalize after the uterus has been evacuated and therefore prompt delivery, often by induction of labor, is advocated. Over a 3-year period, 16 cases (0.35%) of intra-uterine fetal death due to placental abruption occurred at Leiden University Hospital. Five cases were complicated by severe clotting disorders. All women delivered vaginally. No maternal deaths occurred. In contrast to most authors, we present data showing that in four out of five cases the clotting system started to normalize before the uterus was emptied. We suggest that an expectant approach until recovery of the coagulopathy is safer than aiming at a quick delivery. After stabilization of the clotting disorder, one may then consider evacuation of the uterus, if need be by induction of labor.

Maternal hydrops syndrome: a review.

The maternal hydrops syndrome (Ballantyne syndrome, mirror syndrome, pseudotoxemia, triple edema) is a preeclampsia-like disease observed in some pregnancies with severe fetal and/or placental hydrops. We describe three pregnancies with severe immunological fetal-placental hydrops resulting in fetal death, in spite of intrauterine transfusions. The mothers suffered severe hydrops syndrome, one of which was complicated by an eclamptic convulsion. All three women had anemia, low hematocrit, and elevated plasma uric acid levels. It is suggested that low hematocrit is an important pathophysiological feature in maternal hydrops syndrome.

Maternal mortality and its prevention.

Maternal mortality rates in developed countries have declined steeply during the last 50 years. The introduction of sulphonamides and blood transfusion techniques contributed much to lowering maternal mortality rates. The maternal mortality rate in The Netherlands in 1983-1988 was 8.8/100,000 livebirths. In 57% substandard care factors could be identified. This suggests that further improvement in preventing maternal mortality is possible. Maternal mortality rates in developing countries are still unacceptably high as a result of high fertility and a high risk of dying each time a woman becomes pregnant. Complications of illegal abortion are responsible for 25-50% of maternal deaths. Safe contraception could probably result in an important reduction in the number of maternal deaths, but also the provision of accessible maternal health services is essential to reduce maternal mortality in developing countries.

PIP: Physicians analyzed 1983-88 data on 99 maternal deaths in the netherlands to examine causes of death and to what degree substandard care contributed to the deaths. 65 cases were classified as direct maternal deaths, 14 ad indirect maternal deaths, and 20 as fortuitous maternal deaths. They did not include the 20 fortuitous deaths in the maternal mortality rate which stood at 8.8/100,000 live births. The physicians knew all the details in 66 maternal deaths. They identified substandard factors in 57% of these cases. Most of the cases associated with substandard care were women with pregnancy induced hypertension (eclampsia). The substandard care factors included patient or physician's delay, wrong diagnosis, insufficient knowledge of proper treatment, operating without knowledge of clotting disorders, interventions on patients in an unstable condition, inadequate postpartum and postoperative surveillance, and lack of organization. The leading direct cause of maternal death was eclampsia (34%) then thromboembolism (21%), and obstetric hemorrhage (19%). 41% of the women who died from eclampsia also suffered from cerebrovascular hemorrhage. Only 2 women died from septic abortion. The major indirect cause of maternal death was cerebrovascular hemorrhage (57%). Among the direct maternal deaths, 52% had disseminated intravascular coagulation and 25% had a cesarean section. As recently as 1935 in developed countries, puerperal sepsis was the leading cause of maternal deaths (50%) then obstetrical hemorrhage and eclampsia (25%). Mortality rates began to fall with the introduction of sulphonamides and later penicillin. In developing countries, however, maternal mortality remains very high. High rates are due to high fertility and a high risk of death each time a woman is pregnant. Availability of safe contraception and elimination of illegal abortions would reduce maternal mortality considerably.

Transplacental passage of digoxin in severe Rhesus immunization.

Maternal and umbilical vein digoxin concentrations were determined in 16 mothers and fetuses with severe Rhesus-D disease, eight with, and eight without prior digitalization of the mother, when umbilical cord puncture was performed for diagnosis and intrauterine blood transfusion. In the eight patients without digoxin treatment, the digoxin concentrations in both the mother and the umbilical vein were below the limit of detection (less than 0.3 nmol/l). In the other eight patients digitalization of the mother was started 24-48 hours before the first umbilical cord puncture. The maternal and umbilical vein digoxin concentrations were determined on 26 occasions. Except for two instances, digoxin concentrations in the umbilical vein were always below 1 nmol/l. The mean ratio of maternal to fetal digoxin concentrations before initial transfusion was 2.51 ( +/- ISD = 1.47) and before later transfusions 1.67 ( +/- ISD = 0.61). The differences in mean ratios between initial and later transfusions are not significant (p = 0.16). The mean ratio for the total group was 1.93 ( +/- ISD = 1.01). There was no correlation between the maternal to umbilical vein digoxin ratio and either gestational age or umbilical venous hematocrit. The results of our study indicate that the therapeutic effect of transplacental digitalization in severe Rhesus disease is questionable and that a multicentre randomized trial would be necessary to evaluate whether this treatment is of benefit.

Fetal blood group determination in first-trimester pregnancy for the management of severe immunization.

The presence or absence of Rho (D) and Kell antigens on fetal red blood cells was determined in the first trimester of pregnancy on erythrocytes obtained by chorionic villi sampling with the use of mixed agglutination and solid phase microimmunofluorescence techniques. Pregnancies in one Kell-sensitized woman and seven severely RH-sensitized women with a poor obstetric history and a partner heterozygous for the offending antigen were examined. A conclusive diagnosis could be made in seven of the eight cases studied.

Neonatal mortality risk in relation to gestational age and birthweight. Results of a national survey of preterm and very-low-birthweight infants in the Netherlands.

In a cohort of 1338 very preterm and/or very-low-birthweight infants, representing 94% of all infants born alive after less than 32 weeks' gestation or weighing less than 1500 g in the Netherlands in 1983, the neonatal mortality rate was 233 per 1000. In these infants, the best obstetric estimate of gestational age was a better predictor of neonatal mortality than birthweight. In such pregnancies, careful obstetric assessment of gestational age seems to be a more accurate basis for clinical decisions and management than the expected birthweight.