Pre-eclampsia and assisted reproductive technologies: consequences of advanced maternal age, interbirth intervals, new partner and smoking habits.

OBJECTIVE: To examine the risk of pre-eclampsia (PE) in women conceiving after assisted reproductive technologies (ART). Potential confounding from maternal age, long intervals between births, new partner and smoking were evaluated. DESIGN AND SETTING: Population-based cohort study with data from the Medical Birth Registry of Norway. POPULATION: A total of 501,766 mothers with offspring from 1988 to 2009. METHODS: Births to the same mother were linked in sibship data files with information of ART. MAIN OUTCOME MEASURES: Odds ratio (OR) (95% confidence intervals) of PE in pregnancies conceived by ART compared with spontaneous conception, stratified by parity. RESULTS: The prevalence of PE was 5.1% in first, 2.2% in second and 2.1% in third pregnancies. Corresponding figures in ART pregnancies were 6.0%, 3.3% and 4.4%. Hence, the odds ratios of PE in ART pregnancies relative to spontaneous pregnancies increased from 1.2 (1.1-1.3) in first, 1.5 (1.3-1.8) in second to 2.1 (1.4-3.3) in third pregnancies. Adjusting by maternal age lowered the odds ratio to 1.3 (1.1-1.6) and 1.8 (1.2-2.8) in second and third pregnancies, respectively. Multi-adjusted, birth interval had more impact than change of partner. Smoking was associated with a strongly reduced PE risk (odds ratio 0.65; 0.62-0.69), but there was no confounding by smoking on the ART associated risk. CONCLUSIONS: Assisted reproductive technologies increases the risk of PE, and the risk may increase by parity. The association between ART pregnancies and PE is to some extent explained by interbirth intervals and advanced maternal age, but not to change of partner or smoking.

Maternal birth characteristics and perinatal mortality in twin offspring. An intergenerational population-based study in Norway, 1967-2008.

OBJECTIVE: To investigate the relationship between maternal preterm birth and fetal growth in one generation and perinatal mortality of twin offspring in the next generation. DESIGN: Population-based cohort study. SETTING: The Medical Birth Registry of Norway from 1967 to 2008. POPULATION: Linked generational data with 9426 mother-twin pair units. METHODS: Twin offspring were linked to their mothers by means of the unique national identification numbers. MAIN OUTCOME MEASURES: Perinatal mortality in twin offspring. RESULTS: The twin prevalence was not dependent on the mother's gestational age at birth, but increased with increasing birthweight in term mothers. Maternal gestational age was strongly and inversely associated with a risk of perinatal death in one or both of her twin offspring. Compared with term mothers, preterm mothers born at 27-31 and 32-34 weeks had relative risks (RRs) for perinatal loss of 3.83 [95% confidence interval (CI), 1.56-9.36] and 2.41 (95% CI, 1.29-4.50), respectively. This effect was even stronger after the use of assisted reproductive technologies (ART), with a significant interaction between maternal gestational age and ART (P = 0.03). Further, term mothers with birthweight-by-gestational age Z-scores of -2 or less had more than twice the risk of a perinatal loss in their twin offspring relative to mothers with the most favourable birthweight Z-scores (1-1.99) [RR, 2.42 (95% CI, 1.37-4.29)]. CONCLUSIONS: Women born preterm had an increased risk of perinatal mortality in their twin offspring, particularly after ART treatment. The same was true for women who were growth restricted at term. A twin pregnancy is a high-risk pregnancy in general, but even more so if the mother herself was born preterm or was growth restricted at birth.

Trends in incidence and mortality for triplets in Norway 1967-2006: the influence of assisted reproductive technologies.

OBJECTIVE: To assess changes in incidence rates and outcomes of triplets over 40 years with a particular focus on the influence of assisted reproductive technology (ART). DESIGN: Population-based cohort study. SETTING: The Medical Birth Registry of Norway. POPULATION: 2.18 million pregnancies, including 448 sets of triplets and 27,575 twin pairs, covering the years 1967-2006. Since 1988, pregnancies from ART have been available through a separate registry and linked with the birth record. METHODS: Incidence rates and outcomes for triplets were analysed and compared with those for singletons and twins. Relative risks were estimated between time periods and between ART and non-ART pregnancies. MAIN OUTCOME MEASURES: Incidence rates, birthweight, gestational age and perinatal mortality. RESULTS: The total triplet rate per 10,000 pregnancies increased from 1.0 during 1967-71 to 3.5 during 1987-92, followed by a decline to 2.7 during 2002-06. After excluding ART pregnancies, the incidence was more than doubled at the end of the study period. The mean gestational age and birthweight of triplets were significantly lower during 1988-2006 than 1967-87, but similar for ART and non-ART triplets in the last period. The caesarean rate in triplets increased from 47 to 92%. The relative risk of perinatal death in triplets relative to singletons did not change after the introduction of ART [before: relative risk, 8.9 (95% confidence interval, 6.8-11.7); after: relative risk, 10.4 (95% confidence interval, 8.3-13.0)]. CONCLUSIONS: The triplet incidence rate in Norway has more than doubled during the last 40 years, even after excluding ART pregnancies. The risk of perinatal death in triplets is ten times higher relative to singletons and has not changed during this 40-year period, independent of the introduction of ART.

Enzymatic and cellular responses in relation to body burden of PAHs in bivalve molluscs: a case study with chronic levels of North Sea and Barents Sea dispersed oil.

Mytilus edulis and Chlamys islandica were exposed to nominal dispersed crude oil concentrations in the range 0.015-0.25 mg/l for one month. Five biomarkers (enzymatic and cellular responses) were analysed together with bioaccumulation of PAHs at the end of exposure. In both species, PAH tissue residues reflected the exposure concentration measured in the water and lipophilicity determined the bioaccumulation levels. Oil caused biomarker responses in both species but more significant alterations in exposed C. islandica were observed. The relationships between exposure levels and enzymatic responses were apparently complex. The integrated biomarker response related against the exposure levels was U-shaped in both species and no correlation with total PAH body burden was found. For the monitoring of chronic offshore discharges, dose- and time-related events should be evaluated in the selection of biomarkers to apply. From this study, cellular damages appear more fitted than enzymatic responses, transient and more complex to interpret.

Manual removal of the placenta. Incidence and clinical significance.

OBJECTIVE: To determine the incidence and complications related to manual removal of the placenta. METHODS: Review of hospital medical records from 1990 throughout 1994. One thousand five hundred and two vaginal deliveries from 1984 1992 were used for comparisons. RESULTS: A total of 24,750 deliveries were registered during the five year study period. Placenta was removed manually in 165 women (0.6%). The use of general anesthesia for manual removal of placenta decreased from 74% in 1990 to 19% in 1994. Spinal analgesia was applied from 1993, and it was used in 42% of the women in 1994. Of 74 parous women, 12 (16%) had experienced retained placenta before. The average difference in the hemoglobin concentration between the prenatal and the postoperative values was 3.4 g/dl among the patients, and 10% required blood transfusion (1-4 units). Among the controls, there was no decrease in the average hemoglobin concentration, and only 0.5 needed blood transfusion. Endometritis following manual removal was detected in 1.8% of the patients and 1.5% among the controls. Despite manual removal, five women (3%) were considered to have retained placental fragments two days or later after delivery, which required curettage. CONCLUSIONS: Placenta needed to be removed manually in 0.60% of all deliveries in our department. It was associated with increased incidence of hemorrhage and consequently low hemoglobin values. Women with a history of retained placenta have an increased risk of recurrence of retained placenta in subsequent deliveries.

[Intracutaneous injections of sterile water as analgesia during labor]. / Intrakutane injeksjoner med sterilt vann som analgesi ved fødsler.

The author points out that when midwives inject sterile water in the lumbar region as a form of analgesia during the first stage of labour, this may prolong delivery. The author has found no documentation to support this method. The labour lasts almost two hours longer in women receiving such injections. There is no adverse effect on Apgar score after one minute. More investigation is necessary in order to examine the effectiveness and/or adverse effects of method.

[Sterilization of women]. / Sterilisering av kvinner.

PIP: The records of 209 women sterilized in the Lillehammer (Norway) county hospital during the period 1980-82 were examined for age, residence, parity, method of operation, induced abortions and frequency of complications. The patients were sent a questionnaire 6 months after the operation and were asked about how long they had felt unable to work after the operation, whether they regretted the operation, and whether they were satisfied with the cosmetic results. 96% of the patients returned the questionnaires. On the average the women had had 2.4 children at the time of sterilization. Those who had received induced abortions at the same time had 2.5 children. Women resident in the city had 2.1 children, those in the country had 2.4 children. None had 6 children. 20% had received abortion simultaneously. Aside from 1 patient who had transitory paresis in the left arm due to faulty padding in a shoulder support, there were no complications noted in the material. 2 patients regretted the operation. Neither of them had had simultaneous abortion. 1 of these had 1 child. Advised to be sterilized because of severe preeclampsia in her 1st pregnancy, she desired more children. The other, who had 4 children, gave decreased libido as the cause for her regret. Of the 177 who had had laparoscopy, only 6 patients (3.5%) said that they were dissatisfied with the appearance of the scar.^ieng

Lithium and pregnancy. A cohort study on manic-depressive women.

By record linkage of a discharge diagnosis registry and a medical birth registry we identified 350 women with manic-depressive disease who had born a child. The total delivery outcome was poorer than expected with a high perinatal death rate and a high malformation rate. Further studies revealed a high rate of perinatal deaths and/or congenital malformations among infants born of women who had used drugs in early pregnancy, and this phenomenon was concentrated to women who had used lithium and to heart defects. The sample is small, however, and there is no statistically significant difference between delivery outcome in women on lithium and in women on other psychotropic drugs. Until better risk estimates are obtained, lithium should not be used in early pregnancy.