Infant mortality of very preterm infants by mode of delivery, institutional policies and maternal diagnosis.

OBJECTIVE: The aim of this study was to analyse infant mortality among infants born extremely preterm in relation to mode of delivery, maternal diagnosis, and different institutional policies. METHODS: We conducted a national tertiary health care center study using Swedish Medical Birth Register (MBR) data from 1990 to 2002, to examine the 2,094 live births of infants at 23+0 to 27+6 weeks gestation. We assessed the association between mode of delivery, gestational age (GA), calendar year, maternal condition, and institutional policies on infant mortality outcome. RESULTS: At 23-25 weeks, 38% of infants (range: 34-69%) were delivered by cesarean section (CS), while at 26-27 weeks, 66% (59-80%) were delivered by CS. The CS rate for fetal or maternal indications was 98% in cases of pre-eclampsia/eclampsia, 42% for premature rupture of membranes (PROM), 68% for hemorrhage, 76% for PROM+hemorrhage, 56% for breech presentation, and 30% for preterm vertex with no other complications. After cases of pre-eclampsia/eclampsia were excluded, vaginal delivery was associated with a small increase of risk for infant death. Vaginal delivery was associated with a significantly increased risk for infant death in breech presentations and multiple births, while vaginal delivery posed a non-significant risk increase for PROM and hemorrhage. For preterm vertex without any other complications, 4 out of 5 infants were delivered vaginally without any risk increase. CONCLUSION: This study reports high CS rates for very preterm births at Swedish hospitals. In performing CS for very preterm infants, this study suggests a survival advantage for certain maternal conditions, but not for preterm labor with a vertex presentation without other obstetrical complications.

Extremely preterm cesarean delivery: a clinical study.

OBJECTIVES: To describe indications for cesarean section for extremely preterm delivery, peri- and postoperative complications and perinatal outcome. DESIGN: A case-referent study with clinical follow-up. SETTING: A tertiary perinatal center. POPULATION: All deliveries at gestational age <28 weeks at Umeå University Hospital in 1997-2003. For preterm cesarean section referents were women with elective first-time term cesarean section. METHODS: Indications for cesarean section delivery were assessed. Peri- and postoperative complications, asphyxia, and infant survival at discharge were described. RESULTS: The cesarean section rate was 75%, in one third the operation was considered as difficult. Indications for extremely preterm abdominal delivery were severe disease during pregnancy and delivery complications. Six out of ten cesarean sections were performed on fetal indication. Nonisthmic incision was performed in 20% of cases. No major postoperative complications and few minor postoperative complications were noted. Irrespective of mode of delivery, few of the infants had severe asphyxia. CONCLUSION: In balancing the risks of complications related to the surgical procedure against the purported benefits of the infant, this study adds support to the argument to deliver even extremely preterm infants by cesarean section.

Short-term outcome after active perinatal management at 23-25 weeks of gestation. A study from two Swedish tertiary care centres. Part 2: infant survival.

AIM: To determine neonatal survival rates based on both foetal (stillborn) and neonatal deaths among infants delivered at 23-25 wk, and to identify maternal and neonatal factors associated with survival. METHODS: The medical records of 224 infants who were delivered in two tertiary care centres in 1992-1998 were reviewed retrospectively. At these centres, policies of active perinatal and neonatal management were universally applied. Data were analysed by gestational age groups and considered in three time periods. Logistic regression models were used to identify factors associated with survival. RESULTS: The rate of foetal death was 5%. Of infants born alive, 63% survived to discharge. Survival rates including foetal deaths in the denominator at 23, 24 and 25 wk were 37%, 61% and 74%, respectively, and survival rates excluding foetal deaths were 43%, 63% and 77%, respectively. Of infants born with 1-min Apgar scores of 0-1, 43% survived. In the total cohort, survival rates including foetal deaths in the denominator increased from 52% in time period 1 to 61% in time period 2 and 74% in time period 3 (p < 0.02). On multivariate logistic regression analysis, higher birthweight (OR: 1.91 per 100 g increment; 95% CI: 1.45-2.52), female gender (OR: 3.33; 95% CI: 1.65-6.75), administration of antenatal steroids (OR: 2.95; 95% CI: 1.46-5.98) and intrauterine referral from a peripheral hospital (OR: 2.35; 95% CI: 1.18-4.68) were associated with survival. Apgar score < or = 3 at 1 min (OR: 0.46; 95% CI: 0.22-0.95) was associated with decreased survival. The use of antenatal steroids was protective at 23-24 wk (OR: 5.2; 95% CI: 2.0-13.7), but not at 25 wk. CONCLUSIONS: Active perinatal management that included universal initiation of neonatal intensive care virtually eliminated intrapartum stillbirths and delivery room deaths, and resulted in survival rates that compare favourably with those of recent studies. However, the policies of active care postponed death in non-survivors. Individual variations in outcome in relation to the infant's condition at birth as reflected by the Apgar scores preclude the making of treatment decisions in the delivery room.

Short-term outcome after active perinatal management at 23-25 weeks of gestation. A study from two Swedish perinatal centres. Part 3: neonatal morbidity.

AIM: To determine major neonatal morbidity in surviving infants born at 23-25 weeks, and to identify maternal and infant factors associated with major morbidity. METHODS: The medical records of 224 infants who were delivered at two tertiary care centres in 1992-1998 were reviewed retrospectively. At these centres, policies of active perinatal and neonatal management were universally applied. Of the 213 liveborn infants, 140 (66%) survived to discharge. Data were analysed by gestational age and considered in three time periods. Logistic regression models were used to identify factors associated with morbidity. RESULTS: Of the survivors, 6% had intraventricular haemorrhage grade > or = 3 (severe IVH) or periventricular leukomalacia (PVL), 15% retinopathy of prematurity > or = stage 3 (severe ROP) and 36% bronchopulmonary dysplasia (BPD). On logistic regression analysis, severe IVH or PVL was associated with duration of mechanical ventilation (odds ratio, OR: 1.53 per 1-wk increment in duration; 95% confidence interval, CI: 1.01-2.33). Severe ROP was associated with the presence of a patent ductus arteriosus (PDA) (OR: 3.31; 95% CI: 1.11-9.90) and birth in time period 3 versus time periods 1 and 2 combined (OR: 6.28; 95% CI: 2.10-18.74). BPD was associated with duration of mechanical ventilation (OR: 2.71 per 1-wk increment in duration; 95% CI: 1.76-4.18) and with the presence of any obstetric complication (OR: 2.67; 95% CI: 1.07-6.65). Gestational age and birthweight were not associated with major morbidity. Of all survivors, 81% were discharged home without severe IVH, PVL or severe ROP. CONCLUSIONS: Increased survival as a result of active perinatal and neonatal management was associated with favourable morbidity rates compared with those in recent studies. Among survivors born at 23-25 weeks, neither gestational age nor birthweight was a significant determinant of major morbidity.

Short-term outcome after active perinatal management at 23-25 weeks of gestation. A study from two Swedish tertiary care centres. Part 1: maternal and obstetric factors.

AIMS: To provide descriptive data on women who delivered at 23-25 wk of gestation, and to relate foetal and neonatal outcomes to maternal factors, obstetric management and the principal reasons for preterm birth. METHODS: Medical records of all women who had delivered in two tertiary care centres in 1992-1998 were reviewed. At the two centres, policies of active perinatal and neonatal management were universally applied. Logistic regression models were used to identify prenatal factors associated with survival. RESULTS: Of 197 women who delivered at 23-25 wk, 65% had experienced a previous miscarriage, 15% a previous stillbirth and 12% a neonatal death. The current pregnancy was the result of artificial reproduction in 13% of the women. In 71%, the pregnancy was complicated either by pre-eclampsia, chorioamnionitis, placental abruption or premature rupture of membranes. Antenatal steroids were given in 63%. Delivery was by caesarean section in 47%. The reasons for preterm birth were idiopathic preterm labour in 36%, premature rupture of membranes in 41% and physician-indicated deliveries in 23% of the mothers. Demographic details, use of antenatal steroids, caesarean section delivery and birthweight differed between mothers depending on the reason for preterm delivery. Of 224 infants, 5% were stillbirths and 63% survived to discharge. On multivariate logistic regression analysis comprising prenatally known variables, reasons for preterm birth were not associated with survival. Advanced gestational duration (OR: 2.43 per wk; 95% CI: 1.59-3.74), administration of any antenatal steroids (OR: 2.21; 95% Cl: 1.14-4.28) and intrauterine referral from a peripheral hospital (OR: 2.93; 95% CI: 1.5-5.73) were associated with survival. CONCLUSIONS: Women who deliver at 23-25 wk comprise a risk group characterized by a high risk of reproductive failure and pregnancy complications. Survival rates were similar regardless of the reason for preterm birth. Policies of active perinatal management virtually eliminated intrapartum stillbirths.

Snoring, pregnancy-induced hypertension, and growth retardation of the fetus.

STUDY OBJECTIVE: Our purpose was to study the relationship between snoring and pregnancy-induced hypertension and growth retardation of the fetus. DESIGN: Retrospective, cross-sectional, consecutive case series. SETTING: The Department of Gynecology and Obstetrics, University Hospital, Umeâ, Sweden. PARTICIPANTS AND MEASUREMENTS: On the day of delivery, 502 women with singleton pregnancies completed a questionnaire about snoring, witnessed sleep apneas, and daytime fatigue. Data concerning medical complications were taken from the women's casebooks. RESULTS: During the last week of pregnancy, 23% of the women reported snoring every night. Only 4% reported snoring before becoming pregnant. Hypertension developed in 14% of snoring women, compared with 6% of nonsnorers (p < 0.01). Preeclampsia occurred in 10% of snorers, compared with 4% of nonsnorers (p < 0.05). An Apgar score < or = 7 was more common in infants born to habitual snorers. Growth retardation of the fetus, defined as small for gestational age at birth, had occurred in 7.1% of the infants of snoring mothers and 2.6% of the remaining infants (p < 0.05). Habitual snoring was independently predictive of hypertension (odds ratio [OR], 2.03; p < 0.05) and growth retardation (OR, 3.45; p < 0.01) in a logistic regression analysis controlling for weight, age, and smoking. CONCLUSIONS: Snoring is common in pregnancy and is a sign of pregnancy-induced hypertension. Snoring indicates a risk of growth retardation of the fetus.

Survival and 2-year outcome with expectant management of second-trimester rupture of membranes.

OBJECTIVE: To evaluate the perinatal and 2-year outcomes in pregnancies complicated by preterm premature rupture of membranes (PROM) during the second trimester. METHODS: Fifty-three consecutive singleton pregnancies with PROM at 14 to 28 weeks of gestation were studied retrospectively. Management goals were to prolong the pregnancies to 32 weeks through expectant management and to avoid fetal compromise through closer monitoring and active intervention, when necessary, after 23 weeks. Outcome of the surviving infants was based on neurologic, audiometric, and ophthalmologic examinations at 2 years of corrected age. RESULTS: Rupture of membranes occurred at 14-19 weeks (mean 17.4 weeks) in 10 women, at 20-25 weeks (mean 24.0 weeks) in 24, and at 26-28 weeks (mean 27.6 weeks) in 19. The median latency periods to delivery were 72 days, 12 days, and 10 days when rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, respectively. The overall incidence of chorioamnionitis was 28%. There were no fetal deaths and nine neonatal deaths. When rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, the perinatal survival rates were 40%, 92%, and, 100%, respectively. Pulmonary hypoplasia accounted for seven deaths. Of the live-born infants, 81% were alive at 2 years of corrected age. Survival without major impairment was observed in 75%, 80%, and 100% of the survivors when rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, respectively. CONCLUSION: Expectant management of second-trimester PROM offers better perinatal and long-term survival than previously thought.

Preterm premature rupture of membranes and the associated risk for placental abruption. Inverse correlation to gestational length.

OBJECTIVE: To evaluate the association between prolonged premature rupture of membranes (PROM) and placental abruption, especially during midtrimester pregnancy. METHODS: A retrospective hospital based study of 83 women with PROM occurring between 14 and 32 weeks of gestation and where active expectant management was undertaken. RESULTS: Increased frequency of placental abruption was found in patients with early rupture of membranes. The incidence was 50% and 44% when rupture of the membranes occurred before 20 weeks or between 20-24 weeks of pregnancy, respectively. When PROM occurred during gestational ages of 29-32 weeks, the incidence was 13%. Patients with antepartum bleeding, both before (relative risk 34) and after rupture of the membranes (relative risk 38) had a significantly higher risk for placental abruption (p<.001) than women without bleeding prior to delivery. The overall neonatal survival rate was 87%. No neonatal deaths were considered to be directly caused by asphyxia due to placental abruption. CONCLUSION: Using active expectant management and strict routines it seems possible to minimize the risk for perinatal asphyxia and mortality. The clinician should be aware of the significant association between preterm premature rupture of membranes and the risk for subsequent placental abruption, especially in patients with early midtrimester PROM and history of bleedings before rupture of membranes or bleedings during the latency period.

Placental and germ cell alkaline phosphatase RFLPs and haplotypes associated with spontaneous abortion.

Placental alkaline phosphatase (PLAP) and germ cell alkaline phosphatase (GCAP) are controlled by closely linked genes on chromosome 2q34-q37. In previous investigations, associations have been found between PLAP types and spontaneous abortion. In this study, PLAP and GCAP RFLPs and haplotypes were found to show highly significant associations with spontaneous abortions in the Finnish and Swedish populations. However, different associations were found in the Finnish and Swedish populations. The Finnish abortions were associated with the GCAP allele PstI(b) 2 and the Swedish abortions with the PLAP allele PstI(a) 2. A possible mechanism behind the associations may therefore be linkage disequilibria with deleterious alleles within or close to the alkaline phosphatase gene complex.

Vaginal rings for continuous low-dose release of oestradiol in the treatment of urogenital atrophy.

Silicone vaginal rings for the continuous release of 17 beta-oestradiol (E2) with 2 constant in vitro release rates were used for the treatment of symptoms of urogenital atrophy in 2 groups of postmenopausal women. The very low dose of 7 micrograms/24 h was found to alleviate atrophic symptoms effectively and to induce significant maturation of vaginal and urethral epithelium. After a brief initial peak, the serum levels of E2 over 3 mth of treatment remained close to the detection limit. The 'undetectable' E2 release pattern was reflected only in increased levels of oestrone sulphate. There was no evidence of a systemic metabolic response and patient acceptance of the method was excellent. Continuous low-dose release of E2 via vaginal rings consequently offers an alternative means of administering local oestrogen therapy which may be particularly suitable for geriatric patients.

On the value of placental alkaline phosphatase as a marker for gynecological malignancy.

A sensitive catalytic assay for placental alkaline phosphatase (PLAP) was used to quantify enzyme levels in sera from women with malignant gynecological tumors, i.e. cervical carcinoma, ovarian carcinoma and carcinoma of the breast. Values were compared with those of a reference group of 155 healthy individuals. In this group, basic mean levels of the enzyme amounted to 0.06 +/- 0.08 mumoles X min-1 X 1(-1) (mean +/- SD), which corresponds to 0.3 +/- 0.4 ng/ml (mean +/- SD) purified placental alkaline phosphatase. Enzyme levels were not significantly affected by age, whereas sex gave slightly higher values for women in all age groups. This difference was statistically significant (p less than 0.001). The discriminating capacity of PLAP as a tumor marker was analysed with this assay and compared in sensitivity with a radio-immunoassay. A cut-off level of 0.2 mumoles X min-1 X 1(-1), corresponding to 1 ng/ml enzyme protein as measured by the radio-immunoassay, detected 23-68% of the tumor patients, giving false-positive results from the control group in the order of 5%. Corresponding values at a cut-off level of 0.3 mumoles X min-1 X 1(-1) (1.5 ng/ml) gave values 20-44% and 2%, respectively. The present investigation emphasizes that sensitivity in assays of placental alkaline phosphatase, whether catalytic or immunological, must not exceed ng-level.

Placental alkaline phosphatase compared with human placental lactogen and oestriol in high-risk pregnancies.

Serum levels of placental alkaline phosphatase (PLAP), human placental lactogen (HPL) and oestriol (E3) were investigated in 33 women with high-risk pregnancies. In pregnancies complicated by intrauterine growth retardation (IUGR) low PLAP values were constantly recorded. HPL values showed a similar pattern while E3 levels were between normal mean and the lower limit of -2 SD. A clear differentiation between IUGR and pre-eclampsia was achieved by the simultaneous determination of PLAP and HPL. It is suggested that PLAP determinations may be more informative than E3 to detect placental insufficiency.

Placental alkaline phosphatase, alphafetoprotein and carcinoembryonic antigen in testicular tumors. Tissue typing by means of cytologic smears.

Indirect immunofluorescence and radioimmunoassay with specific rabbit antisera demonstrated the occurrence of alphafetoprotein (AFP), carcinoembryonic antigen (CEA) and placental alkaline phosphatase (PLAP) in primary testicular tumor cells. Embryonal carcinomas had AFP- and CEA-containing cells, sometimes PLAP. PLAP and sometimes CEA were found in seminoma cells. Sera from patients with advanced non-seminomatous tumors could contain any of these antigens or any combination of them. Sera from patients with seminomas had raised PLAP or CEA. PLAP appears to be a new marker for seminoma.

Serum levels of placental alkaline phosphatase in high-risk pregnancies.

A recently developed radioimmunoassay (RIA) for placental alkaline phosphatase (paf) was used to estimate the maternal serum levels of the enzyme in 51 women with various complications of pregnancy. The results were compared with a reference group of 242 women with apparently normal pregnancies. Women with intrauterine growth retardation (IUGR) or severe or mild preeclampsia had significantly low weight of the fetoplacental unit. Simultaneous determinations of PAF in maternal serum and the urinary total estrogen/24 hr gave a clear differentiation of the IUGR group from the other pregnancies at risk. All PAF values from risk pregnancies were below the mean values of normal pregnancy.

Catalytic properties and stability of three common variants of placental alkaline phosphatase.

Three placental alkaline phosphatases purified to homogeneity, i.e., the F, I, and S variants, were investigated for catalytic and stability properties. All three forms of the enzyme were found to have almost identical pH optima (10.7--10.8), similar sensitivity to the uncompetitive inhibitors L-phenylalanine (70%) and L-leucine (30%), and identical Km values against p-nitrophenylphosphate, beta-glycerophosphate, and alpha-naphthylphosphate. Significant differences among the three types were observed in thermal stability. The F variant was found to be most stable and the I variant most labile at 79 C. At 70 C all three forms were stable.

A double antibody solid phase radioimmunoassay for placental alkaline phosphatase.

A solid-phase "direct" radioimmunoassay for determination of placental alkaline phosphatase in serum was developed. The assay is highly sensitive, with a minimum detectable dose of 9 ng protein per ml. The specificity for the placental type of the enzyme, in comparison to other serum alkaline phosphatases, was found to be convincing. The choice of genetic types of either placental alkaline phosphatase or antiserm was found not to influence the radioimmunoassay. With the described technique the serum concentration of this enzyme during normal pregnancy was measured. A 25-fold increase from low levels during the first trimester up to 252 +/- 70 ng/ml (mean +/- S.D.) in gestation week 40 was observed.

Purification and partial characterization of the I variant of placental alkaline phosphatase.

The I variant of placental alkaline phosphatase was purified to homogeneity by means of DEAE-cellulose chromatography, isoelectric focusing, and gel filtration on AcA-34. The specific activity of the I variant was found to be 3.33 micronkat/mg. The enzyme is a dimer with an isoelectric point of 4.6 and a molecular weight of 120,000 as determined by sodium dodecylsulfate electrophoresis. The amino acid composition and other physiocochemical properties of the I variant were compared with those of the more common F and S variants. The low activity associated with the I variant is apparently not due to a low specific activity, but to decreased molecular stability. The behavior in the ultracentrifuge and other observations suggest that the I variant differs from the F and S variants in surface charge distribution.

Purification and parital characterization of two genetic variants of placental alkaline phosphatase.

The two most common variants of placental alkaline phosphatase, the F and S variants, were purified to homogeneity and characterized. Their molecular weights were determined by equilibrium ultracentrifugation and sodium dodecylsufate polyacrylamide gel electrophoresis, which gave almost identical values for the two variants, 118,000 (F) and 119,000 (S). The amino acid compositions of F and S variants presented here are found to be very similar. Differences between the two variants were found in specific activity (160 U/mg for F and 250 U/mg for S), isoelectric point (IP - 4.5 for F and 4.7 for S), sedimentation coefficient (6.5 X 10(-13) sec for F and 6.4 X 10(-13) sec for S). Thus the structural differences observed for these enzyme variants seem to affect both the active site and the protein conformation.