Mika Nuutila

Clinical presentation and risk factors of placental abruption

Background. To study the risk factors of placental abruption during the index pregnancy. Methods. One hundred and ninety‐eight women with placental abruption and 396 control women were identified among 46,742 women who delivered at a tertiary referral university hospital between 1997 and 2001. Clinical variables were compared between the groups. Multivariate logistic regression analysis was applied to identify independent risk factors. The clinical manifestations of placental abruption were also studied. Results. The overall incidence of placental abruption was 0.42%. The independent risk factors were maternal (adjusted OR 1.8; 95% CI 1.1, 2.9) and paternal smoking (2.2; 1.3, 3.6), use of alcohol (2.2; 1.1, 4.4), placenta previa (5.7; 1.4, 23.1), pre‐eclampsia (2.7; 1.3, 5.6), and chorioamnionitis (3.3; 1.0, 10.0). Vaginal bleeding (70%), abdominal pain (51%), bloody amniotic fluid (50%), and fetal heart rate abnormalities (69%) were the most common manifestations. Neither bleeding nor pain was present in 19% of the cases. Overall, 59% had preterm labor (OR 12.9; 95% CI 8.3, 19.8), and 91% were delivered by cesarean section (34.7; 20.0, 60.1). Of the newborns, 25% were growth restricted. The perinatal mortality rate was 9.2% (OR 10.1; 95% CI 3.4, 30.1). Retroplacental blood clot was seen by ultrasound in 15% of the cases. Conclusions. Maternal alcohol consumption and smoking, and smoking by the partner turned out to be independent risk factors for placental abruption. Smoking by both partners multiplied the risk. The liberal use of ultrasound examination contributed little to the management of women with placental abruption.

Prepregnancy risk factors for placental abruption

Background. To define the prepregnancy risk factors for placental abruption. Methods. One hundred and ninety‐eight women with placental abruption and 396 control women without placental abruption were retrospectively identified among 46,742 women who delivered at a tertiary referral university hospital between 1997 and 2001. Relevant historical and clinical variables were compared between the groups. Multivariate logistic regression analysis was applied to identify independent risk factors. Results. The overall incidence of placental abruption was 0.42%. Placental abruption recurred in 8.8% of the cases. The independent risk factors were smoking (OR 1.7; 95% CI 1.1, 2.7), uterine malformation (OR 8.1; 1.7, 40), previous cesarean section (OR 1.7; 1.1, 2.8), and history of placental abruption (OR 4.5; 1.1, 18). Conclusions. Although univariate analysis identified many risk factors, only smoking, uterine malformation, previous cesarean section, and history of placental abruption remained significant after multivariate analysis, increasing the risk of placental abruption in subsequent pregnancy. It may be possible to approximate the risk for placental abruption based on these simple prepregnancy risk factors.

Phosphorylated isoforms of insulin-like growth factor binding protein-1 in the cervix as a predictor of cervical ripeness.

OBJECTIVE To study the isoforms of insulin-like growth factor binding protein-1 (IGFBP-1) in cervical secretion and to evaluate whether their assessment could serve in prediction of cervical ripeness at term. METHODS We measured the concentrations of IGFBP-1 in cervical swab samples of 64 women scheduled for labor induction by amniotomy or cervical ripening with prostaglandin E2 gel. Two immunoenzymometric assays were used: a previously described assay 1, which detects the nonphosphorylated and lesser phosphorylated isoforms, and a novel assay 2, which detects the lesser and highly phosphorylated isoforms of IGFBP-1. A set of 39 amniotic fluid (AF) samples also was analyzed to compare the phosphorylation status of IGFBP-1 in cervical secretion with that in AF. RESULTS In all cervical samples, IGFBP-1 concentration was higher by assay 2 than by assay 1, whereas in all AF samples, the results were the opposite. Initially, the median IGFBP-1 concentration in the ripe cervices (Bishop scores 6 or greater; n = 29) was approximately four times as high as that in the unripe cervices (Bishop scores 5 or less; n = 35). The cervical IGFBP-1 concentrations increased eight-fold in 6 hours after the first application of PGE2. CONCLUSION Phosphorylated isoforms of IGFBP-1, different from those in AF, are present in the cervical secretion of women with intact fetal membranes and reflect cervical ripeness. A bedside test for those IGFBP-1 isoforms might help in predicting amenability for labor induction.

Parvovirus B19 Infection in Fetal Deaths

BACKGROUND Parvovirus B19 infection during pregnancy can lead to nonimmune fetal hydrops, miscarriage, and intrauterine fetal death (IUFD). Some studies have suggested that parvovirus B19 infection may surprisingly often result in nonhydropic fetal death during the third trimester, in the absence of maternal serological evidence of acute infection. This study was conducted to investigate the prevalence of parvovirus B19 DNA among fetuses from miscarriages and IUFDs. METHODS We retrospectively studied 535 unborn fetuses, including 120 fetuses from miscarriages and 169 from IUFDs. The control fetuses were 246 fetuses from induced abortions. All fetuses were autopsied from July 1992 through December 1995 and from January 2003 through December 2005 in Helsinki, Finland. The period included a major epidemic of parvovirus B19 infection in 1993. Formalin-fixed, paraffin-embedded fetal tissues were studied with use of a highly sensitive and specific PCR that was capable of detecting all 3 parvovirus B19 genotypes and by histologic examination. In addition, maternal parvovirus B19 serological status was determined. RESULTS Parvovirus B19 DNA was detected in 5 fetuses with gestational ages of 14, 22, 23, 30, and 39 weeks; these included fetuses from 4 (2.4%) of the 169 IUFDs and 1 (0.8%) of the 120 miscarriages. During the epidemic year 1993, the prevalence of parvovirus B19 DNA-positive fetal deaths was 6 times the prevalence during nonepidemic years. All 5 mothers of the parvovirus B19 DNA-positive fetuses had serological signs of acute parvovirus B19 infection close to the time of fetal death. The only nonhydropic fetus was full-term. CONCLUSIONS Our findings indicate that the prevalence of parvovirus B19 infection among fetuses from IUFDs is low. In particular, our findings did not verify the claimed high prevalence of third-trimester nonhydropic IUFDs associated with parvovirus B19.

Are health expectations of term breech infants unrealistically high

Background.  The aim of this study was to compare the effect of fetal presentation and mode of delivery on infant outcome in a nation‐wide study.

Decreasing perinatal mortality in placental abruption.

Objective. To study perinatal mortality associated with placental abruption. Design. Retrospective population study using the Finnish Hospital Discharge Register and Medical Birth Register data. Setting. Finland, 1987–2005. Population. Pregnancies with placental abruption and all other births without placental abruption. Methods. The national Hospital Discharge Register and Medical Birth Register were used to identify all pregnancies with placental abruption. Demographic data and delivery outcomes were collected retrospectively. Perinatal mortality associated with placental abruption was compared with that in other births. Potential risk factors were analysed. Main outcome measures. Perinatal mortality in placental abruption. Results. The study consisted of 618 735 women with 1.14 million pregnancies, 4336 of whom had placental abruption. Overall perinatal mortality with abruption was 119 per 1000 births. Placental abruption explained 7% of all perinatal deaths. The mortality among singleton births (125 per 1000) was higher than among multiple births (40 per 1000). The majority of deaths (77%) occurred in utero. Singleton perinatal mortality with abruption decreased from 173 per 1000 in 1987–1990 to 98 per 1000 in 2000–2005 (p < 0.001). In singleton births at <32 gestational weeks, overall perinatal mortality was high (345 per 1000) and was not increased by placental abruption. Prematurity, low birthweight, male fetal sex and maternal smoking were independent risk factors for placental abruption‐related perinatal mortality. Conclusions. Although mortality associated with placental abruption decreased during the study period, placental abruption still remains an important cause of perinatal mortality.

Maternal deaths in Finland: Focus on placental abruption

Objective. To study placental abruption‐associated maternal deaths out of all maternal deaths in Finland. Design. Register‐based study. Setting. The Finnish Medical Birth Register (MBR), the Hospital Discharge Register (HDR), and the Cause‐of‐Death Register data during 1972–2005. Methods. The maternal deaths were identified by linking data from the MBR, the HDR, and the Cause‐of‐Death Register. The clinical data were collected from the case records and death certificates. Main outcome measures. Cause‐specific maternal death with special reference to placental abruption. Results. During the study period, a total of 2,104,436 live births and 117 direct maternal deaths (caused by a disease or its management unique to the pregnancy) occurred in Finland. The direct maternal mortality ratio (MMR) was 5.6 per 100,000 live births. The two leading causes were thromboembolism (24.0%) and hemorrhage (22.3%) representing almost half of all maternal deaths. Altogether 7,735 placental abruptions were identified with three maternal deaths giving a case fatality rate of 0.4 per 1,000 cases. The MMR (38.8 per 100,000) was nearly seven times higher than the overall MMR (5.7 per 100,000) (p = 0.010). Conclusion. The direct MMR in Finland is at the level generally seen in Western Europe. The main causes to maternal death are thromboembolism and obstetric hemorrhage. Deaths to placental abruption are rare, but still seven times higher than the overall MMR.

Cervical nitric oxide release in women postterm.

OBJECTIVE: Nitric oxide may be a factor in cervical ripening. We compared the nitric oxide metabolite levels in cervical fluid in women going beyond term and in women delivering spontaneously at term. METHODS: We studied a total of 208 women with singleton pregnancies: 108 women who went beyond term (294 days or longer), and 100 women who went spontaneously into labor at term. Cervical fluid samples, collected well before the initiation of labor, were assessed for nitric oxide metabolites using an assay with a detection limit of 3.8 μmol/L. RESULTS: Women going beyond term had detectable levels of nitric oxide metabolites in their cervical fluid (60%) less often (P = .001) than women delivering at term (87%). The nitric oxide metabolite concentration in cervical fluid in women going beyond term (median 23.5 μmol/L; 95% confidence interval less than 3.8, 31.8) was 4.5 times lower (P < .001) than that in women delivering at term (median 106.0 μmol/L; 95% confidence interval 81.8, 135.0). Such a difference (14.0 versus 106.0 μmol/L) also existed when only the 66 women going into spontaneous postterm labor were included in the comparison. Both nulliparous (median less than 3.8 μmol/L) and parous (median 31.3 μmol/L) women going beyond term had lower (P < .01) cervical fluid nitric oxide metabolite levels than nulliparous and parous women delivering at term (medians 76.1 and 101.3 μmol/L, respectively). In the postterm group, women with cervical fluid nitric oxide metabolite concentrations at or below the median failed more often (P < .001) to progress in labor and had longer (P = .02) duration of labor than those with cervical fluid nitric oxide metabolite concentrations above the median. CONCLUSION: Reduced cervical nitric oxide release may contribute to prolonged pregnancy. LEVEL OF EVIDENCE: II-2

Local administration of prostaglandin E2 for cervical ripening and labor induction: the appropriate route and dose

Background. Although there are many comparative studies concerning the local administration of prostaglandin E2 gel for cervical ripening and labor induction, the safety, efficacy and the appropriate route and dose of the gel are still debated.

Self-reported smoking habits and serum cotinine levels in women with placental abruption

Objective. Smoking is an important risk factor for placental abruption with strong dose‐dependency. Pregnant smokers often underreport tobacco use which can be objectively assessed by measuring serum cotinine levels. We examined the accuracy between self‐reported smoking habits and early pregnancy serum cotinine levels in women with or without placental abruption. Design. Retrospective case‐control study. Setting. University Hospital. Population. A total of 175 women with placental abruption and 370 control women. Methods. Serum samples collected during the first trimester were analyzed for serum cotinine levels. Cotinine concentration over 15 ng/ml was considered as the cutoff indicating active smoking. Smoking habits of the women and their partners were recorded at the same visit. Main outcome measure. Placental abruption. Results. Of the cases of women with placental abruption, 27.4% reported smoking compared with 14.3% of the controls (p < 0.001). Based on serum cotinine levels, 30.3% of the case women and 17.6% of the control women were considered smokers (p = 0.003). Serum cotinine levels among smokers were higher in the abruption group than in the control group (median 229.5 ng/ml (interquartile range 169.8–418.1) vs. 153.5 ng/ml (56.6–241.4), p = 0.002). Self‐reported number of cigarettes smoked daily correlated well with the cotinine levels (r = 0.68, p < 0.001). Of the women reporting as nonsmokers, approximately 7% were considered smokers based on cotinine testing. Conclusion. Pregnant women with subsequent placental abruption are heavier smokers than pregnant control women. Self‐reported smoking habits correlate well with serum cotinine levels in Finland. Therefore, self‐reported smoking can be considered as a risk marker for placental abruption.