Inter-hospital variation in use of obstetrical blood transfusion: a population-based cohort study.

OBJECTIVE: To identify the extent of hospital-to-hospital variation in use of obstetrical blood transfusion. DESIGN: Population-based cohort study linking provincial perinatal and blood transfusion registries. SETTING: British Columbia, Canada, 2004-2015. POPULATION: All pregnant women delivering at or beyond 20 weeks' gestation at any British Columbia hospital. METHODS: Mixed-effects regression models were used to estimate hospital-specific transfusion rates after sequentially accounting for (1) the role of random variation, (2) maternal medical and obstetrical characteristics (i.e. patient case mix) and (3) institutional and delivery factors (such as use of instrumental or caesarean delivery). MAIN OUTCOME MEASURES: Hospital-specific use of obstetrical red blood cell transfusion. RESULTS: Among 44 hospitals, crude institutional transfusion rates across the study period ranged from 3.7 to 23.6 per 1000, with an average of 8.3 per 1000. After adjusting for maternal characteristics, institution and delivery risk factors, a nearly three-fold difference in rates between the 10th and 90th percentile remained (5.4-14.5 per 1000). Twelve sites had rates significantly higher or lower than the provincial average. Women residing in remote areas were 2.5-fold (95% CI 1.8-3.5] more likely to receive a blood transfusion than were women residing in metropolitan areas. CONCLUSIONS: Meaningful variation between hospitals in use of blood transfusion during pregnancy was not explained by differences in patient case-mix or institutional factors, suggesting that over- or under-utilisation of this resource may be occurring in obstetrical care. TWEETABLE ABSTRACT: Use of blood transfusion in pregnant women varied broadly between hospitals in British Columbia, Canada.

Perinatal and maternal morbidity and mortality among term singletons following midcavity operative vaginal delivery versus caesarean delivery.

OBJECTIVE: To quantify severe perinatal and maternal morbidity/mortality associated with midcavity operative vaginal delivery compared with caesarean delivery. DESIGN: Population-based, retrospective cohort study. SETTING: British Columbia, Canada. POPULATION: Term, singleton deliveries (2004-2014) by attempted midcavity operative vaginal delivery or caesarean delivery in the second stage of labour, stratified by indication for operative delivery (n = 10 901 deliveries; 5057 indicated for dystocia, 5844 for fetal distress). METHODS: Multinomial propensity scores and mulitvariable log-binomial regression models were used to estimate adjusted rate ratios (ARR) and 95% confidence intervals (95% CI). MAIN OUTCOME MEASURES: Composite severe perinatal morbidity/mortality (e.g. convulsions, severe birth trauma and perinatal death) and severe maternal morbidity (e.g. severe postpartum haemorrhage, shock, sepsis and cardiac complications). RESULTS: Among deliveries with dystocia, attempted midcavity operative vaginal delivery was associated with higher rates of severe perinatal morbidity/mortality compared with caesarean delivery (forceps ARR 2.11, 95% CI 1.46-3.07; vacuum ARR 2.71, 95% CI 1.49-3.15; sequential ARR 4.68, 95% CI 3.33-6.58). Rates of severe maternal morbidity/mortality were also higher following midcavity operative vaginal delivery (forceps ARR 1.57, 95% CI 1.05-2.36; vacuum ARR 2.29, 95% CI 1.57-3.36). Among deliveries with fetal distress, there were significant increases in severe perinatal morbidity/mortality following attempted midcavity vacuum (ARR 1.28, 95% CI 1.04-1.61) and in severe maternal morbidity following attempted midcavity forceps delivery (ARR 2.34, 95% CI 1.54-3.56). CONCLUSION: Attempted midcavity operative vaginal delivery is associated with higher rates of severe perinatal morbidity/mortality and severe maternal morbidity, though these effects differ by indication and instrument. TWEETABLE ABSTRACT: Perinatal and maternal morbidity is increased following midcavity operative vaginal delivery.

Timing of delivery for pregnancies with congenital diaphragmatic hernia.

A recent report has suggested that delivery at early term ages may be associated with lower mortality among infants with congenital diaphragmatic hernia. We sought to confirm this finding by examining gestational age-specific mortality in the USA in term infants with isolated congenital diaphragmatic hernia, delivered following the spontaneous onset of labour. In the final population of 928 infants, neonatal and infant mortality decreased with advancing gestation, from 25 and 36% at 37 weeks of gestation, respectively, to 17 and 20% at 40 weeks of gestation, respectively. Log-binomial regression models showed that neonatal and infant mortality at 37 weeks of gestation were significantly higher than at 40 weeks. Further evidence, ideally from a randomised trial, is needed before recommendations for clinical practice on timing of delivery should be made.

Do commonly used oral antihypertensives alter fetal or neonatal heart rate characteristics? A systematic review.

OBJECTIVE: To examine fetal (FHR) and neonatal heart rate patterns following use of common oral antihypertensives in pregnancy. METHODS: A systematic review of randomized controlled trials (RCTs), observational studies (N >/= 6 women), and animal studies. Data were abstracted (two reviewers) to determine relative risk (RR) (or risk difference (RD) for low event rates) and 95% CI. RESULTS: Eighteen RCTs (1858 women), one controlled observational study (N = 22), and seven case series (N = 117) were reviewed. Most hypertension was pregnancy-induced (N = 14 studies). The FHR was assessed by cardiotocogram (CTG) (N = 17 studies (visual interpretation); 1 study (computerized CTG), or umbilical artery velocimetry (N = 4). Four studies examined neonatal heart rate. In placebo-controlled RCTs (N = 192 women), adverse FHR effects did not differ between groups [9/101 (drugs) vs. 7/91 (placebo); RD 0.02, 95% CI (- 0.06, 0.11); chi2 = 1.02]. In six drug vs. drug RCTs (295 women), adverse FHR effects did not differ between groups [29/144 (methyldopa) vs. 42/151 (other drugs); RR 0.72, 95% CI (0.49, 1.07); chi2 = 0.69]. In one labetalol vs. placebo trial, neonatal bradycardia did not differ between groups [4/70 (labetalol) vs. 4/74 (placebo); OR 1.06, 95% CI (0.26, 4.39)], while in three drug vs. drug RCTs, neonatal bradycardia was not observed (0/24 vs. 0/26). CONCLUSIONS: Available data are inadequate to conclude whether oral methyldopa, labetalol, nifedipine, or hydralazine adversely affect fetal or neonatal heart rate and pattern. Until definitive data are available, FHR changes cannot be reliably attributed to drug effect, but may be due to progression of the underlying maternal or placental disease.

Immediate and short-term effects of pulmonary artery banding on left ventricular performance in foetal sheep.

AIM: To evaluate foetal left ventricular performance when its preload was increased by banding the pulmonary artery, a study design where a simultaneous change in left ventricular afterload is unlikely. METHODS: Nine ovine foetuses were studied with real-time images and Doppler echocardiography before, 3-4 and 6-8 d after surgery. Seven of these foetuses were also studied during the surgical intervention, immediately before and within 2 min after banding. RESULTS: The immediate effects of a 90-95% reduction of the pulmonary artery cross-sectional area were: a 53 +/- 20% (mean +/- SD) decrease and a 38 +/- 10% increase of right (RvQ) and left ventricular output (LvQ), respectively. Comparing measurements before and 3-4 d after operation, there was a 64 +/- 16% decrease of RvQ and a 64 +/- 25% increase of LvQ. The increase in LvQ was due to an increase in both heart rate (19 +/- 10%) and stroke volume (38 +/- 18%). After an additional 3-4 postoperative days, heart rate remained increased to the same extent, but there was a more pronounced increase of LvQ (93 +/- 19%) and stroke volume (59 +/- 22%). CONCLUSION: The parallel foetal circulation has a capacity to handle a severely increased afterload for the right ventricle by immediately improving and maintaining an increased left ventricular performance. This improvement was in part accomplished by an increase in stroke volume.

Changes in flow velocity patterns of the superior and inferior venae cavae during placental circulatory insufficiency.

OBJECTIVES: Placental circulatory insufficiency, expressed by the disappearance of the diastolic component of the umbilical artery Doppler velocity waveforms, causes blood flow redistribution that could disturb, to different extents, the systemic venous returns to the heart. The purpose of this study was to investigate the effect of an absence of diastolic blood flow in the umbilical artery on the relationship between the Doppler flow velocities of the venae cavae. METHODS: Fifteen normal fetuses (normal group) were matched for gestational age with 11 fetuses with absent diastolic flow in the umbilical artery (abnormal group). In the venae cavae, the following Doppler variables were measured and compared between groups: (a) during ventricular systole: maximum (S(max)) and minimum velocities (S(min)) and velocity integrals (SI); (b) during ventricular diastole: peak velocity of the E-wave and its integral (EI), the A-wave and its integral (AI). A venous velocity index (VVI) was defined as (S(max) + S(min))/S(max). RESULTS: In the normal group, S(min) and VVI were significantly higher in the inferior vena cava (IVC) than in the superior vena cava (SVC). The ratio SVC-VVI/IVC-VVI was therefore always less than one. In the abnormal group, S(min), SI, E, EI and VVI were higher in the SVC compared to those of the IVC. The ratio SVC-VVI/IVC-VVI was always greater than one. CONCLUSION: In the absence of umbilical artery diastolic flow, a reciprocal shift is observed between the IVC and SVC velocity waveforms characterized by a flow profile in the IVC which resembles that of a normal SVC profile and vice versa. These changes are another manifestation of blood flow redistribution towards the brain in the presence of placental circulatory insufficiency. They should be taken into account on Doppler assessment of ventricular diastolic function based on venous flow patterns during placental circulatory impairment.

Characterization of PGE2 receptors in fetal and newborn lamb ductus arteriosus.

Although the role of PGE2 in maintaining ductus arteriosus (DA) patency is well established, the specific PGE2 receptor subtype(s) (EP) involved have not been clearly identified. We used late gestation fetal and neonatal lambs to study developmental regulation of EP receptors. In the fetal DA, radioligand binding and RT-PCR assays virtually failed to detect EP1 but detected EP2, EP3D, and EP4 receptors in equivalent proportions. In the newborn lamb, DA total density was one-third of that found in the fetus and only EP2 was detected. Stimulation of EP2 and EP4 increased cAMP formation and was associated with DA relaxation. Though stimulation of EP3 inhibited cAMP formation, it surprisingly relaxed the fetal DA both in vitro and in vivo. This EP3-induced relaxation was specifically diminished by the ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide. In conclusion, PGE2 dilates the late gestation fetal DA through pathways that involve either cAMP (EP2 and EP4) or K(ATP) channels (EP3). The loss of EP3 and EP4 receptors in the newborn DA is consistent with its decreased responsiveness to PGE2.

Correlation between prenatal velocity waveforms in the aortic isthmus and neurodevelopmental outcome between the ages of 2 and 4 years.

OBJECTIVE: Experimental studies on fetal lambs have shown that during an increase in the resistance to placental flow the delivery of oxygen to the brain is preserved as long as net flow through the aortic isthmus is antegrade. Our purpose was to determine whether the same changes in aortic isthmus flow in human subjects have any impact on neurodevelopmental outcome. STUDY DESIGN: Forty-four fetuses were retrospectively included in this study on the basis of an abnormal Doppler velocity in the umbilical artery. Mean gestational age at delivery was 33.0 +/- 2.0 weeks and mean birth weight 1386 +/- 435 g. The neurodevelopmental condition was assessed between the ages of 2 and 4 years. The developmental score was analyzed in relation to the flow patterns in the fetal aortic isthmus, which were classified as follows: group A, net isthmic flow antegrade (defined as the ratio of the systolic antegrade to the diastolic retrograde velocity integrals) (n = 39); group B, net isthmic flow retrograde (n = 5). RESULTS: Nonoptimal neurodevelopment was observed in 19 (49%) of 39 fetuses in group A and in all 5 fetuses (100%) in group B. This difference is significant and leads to a relative risk of 2.05 (95% confidence interval, 1.49-2.83) for neurodevelopmental deficit when predominantly retrograde flow is observed in the fetal aortic isthmus before birth. CONCLUSION: Measuring the ratio of antegrade to retrograde velocity integrals in the aortic isthmus could help in the indirect assessment of cerebral oxygenation during placental circulatory insufficiency.

Generation of reactive O2 species in the myocardium of newborn lambs following intrauterine increase in right ventricular pressure.

Fetuses with pulmonary stenosis and constriction of the ductus arteriosus or the recipient twin in the context of a twin-to-twin transfusion syndrome may present with severe right ventricular myocardial dysfunction. Free O2 radicals are known to be increased in hypertrophied adult myocardium secondary to an increase in endocavitary pressure. This study investigates whether products of reactive O2 species generation are abnormally elevated in the myocardium of fetuses with increased right ventricular pressure. Banding of the main pulmonary artery was performed in five fetal lambs at 90 to 100 days of gestation. Three other animals had a sham intervention and were used as controls. Postoperative observation lasted on average 42 days (range 33-49 days). The levels of hydroperoxides were found to be significantly higher in the right ventricle of the stenosed lambs (6.6 +/- 3.5 nmol/mg protein) compared to the left ventricle of the same lambs (0.7 +/- 0.7 nmol/mg protein), and compared to the right (0.12 +/- 0.1 nmol/mg protein) and the left (0.5 +/- 0.8 nmol/mg protein) ventricles of the controls. It is concluded that during fetal life, an increase in right ventricular pressure is associated with a marked accumulation of products of reactive O2 species generation in the right ventricular myocardium.

Correlation between electrocardiographic and ultrasonographic time-interval measurements in fetal lamb heart.

The objective of this study was to establish the echocardiographic modality that best correlates with electrical events in the fetal heart. No documentation on the relationship between electrical events recorded with a surface ECG and fetal M-mode or Doppler echocardiographic measurements is available. The following ultrasound tracings were recorded simultaneously with a surface ECG on six exteriorized near-term fetal lambs: 1) M-mode echocardiography of atrial and ventricular contractions; and 2) Doppler flow velocity waveforms in the right superior vena cava (SVC) either alone or 3) in association with those of the ascending aorta. In the SVC, the onset of the retrograde A wave and the beginning of the forward wave during ventricular systole were used as markers for the start of the P wave and QRS complex, respectively. For the simultaneous SVC and ascending aorta tracings, the beginnings of the A and of the aortic ejection waves were used as markers. On average, the atrioventricular interval was 84 ms longer than the PR interval with the M-mode, corresponding to an increase of 107%. A similar observation was made for the simultaneous Doppler signals from SVC and ascending aorta, but the difference between the atrioventricular and PR intervals was smaller, averaging 35 ms. When the SVC Doppler was taken alone, no significant difference was found between atrioventricular and ventriculoatrial compared with PR and RP intervals, respectively, and a strong correlation was found between the two methods of measurement, both for the atrioventricular (r = 0.91) and ventriculoatrial (r = 0.89) intervals. Doppler interrogation of the SVC alone and, to a lesser degree, of the SVC and ascending aorta are reliable indirect markers for the timing of electrical events of the fetal lamb heart in sinus rhythm.

Relationship between flow through the fetal aortic isthmus and cerebral oxygenation during acute placental circulatory insufficiency in ovine fetuses.

OBJECTIVE: We sought to investigate whether the reversal of blood flow through the aortic isthmus, as observed during an increase in placental vascular resistance, could be responsible for a significant fall in oxygen delivered to the fetal brain. STUDY DESIGN: With the appearance of reverse flow in the aortic isthmus, preplacental blood with low oxygen saturation could contaminate the ascending aorta blood destined for the brain. Stepwise compression of the umbilical veins of 8 exteriorized fetal lambs was realized at approximately 140 days of gestation. Four other animals were used as controls. Flows through the aortic isthmus and both carotid and umbilical arteries were measured by Doppler echocardiography in the basal state (hemodynamic class 1) and during moderate (class 2), severe (class 3), and extreme (class 4) increases in resistance to placental flow. Oxygen delivered to the brain was calculated from carotid blood flow and oxygen content. RESULTS: In the control group no change was noted in umbilical and carotid arteries or in the aortic isthmus blood flow. Oxygen delivered to the brain remained stable. In the study group the increase in resistance to placental flow caused a significant fall in umbilical flow and carotid oxygen content, while blood flow in the carotid arteries increased slightly. The values for aortic isthmus flow and oxygen delivered to the brain during the 4 hemodynamic classes were, on average, as follows: class 1, 98.2 and 2.9 mL/(min x kg); class 2, 52.8 and 3.1 mL/(min x kg); class 3, 3.7 and 2.6 mL/(min x kg); and class 4, -29.8 and 0.7 mL/(min x kg), respectively. CONCLUSION: During an acute increase in placental vascular resistance, delivery of oxygen to the brain is preserved despite a significant drop in arterial oxygen content as long as net flow through the isthmus is anterograde.

Rapid detection of CYP1A1, CYP2D6, and NAT variants by multiplex polymerase chain reaction and allele-specific oligonucleotide assay.

Drugs and carcinogens are excreted from the body after metabolic conversion involving enzymes mediating oxidative metabolism and conjugation. Many of the corresponding genes exhibit functional polymorphisms that contribute to individual cancer susceptibility. To increase the efficiency and to facilitate genotyping, we developed a combined approach (PCR-ASO) which includes multiplex PCR and allele-specific oligonucleotide (ASO) hybridization. PCR primer pairs were used to amplify the following alleles/variants: CYP1A1*1, *2A, *2B; CYP2D6*3, *4; NAT1*4, *3, *10, *11, *14, *15; and NAT2*4, *5A, *5B, *5C, *6A, *7B. The products were dot-blotted and polymorphisms were detected by hybridization with ASO probes for both wild-type and variant sites in parallel. This approach was validated by genotyping DNA samples from a French-Canadian population that was previously analyzed by PCR-RFLP. The variants frequencies were compared with the data on other populations available in the literature. The PCR-ASO assay appears to be simple, efficient, and cost-effective, particularly if a large number of samples are to be screened for several DNA variants. This approach has potential for automation with microplates and robotic workstations for high throughput.

Circulatory changes induced by isovolumic increase in red cell mass in fetal lambs.

AIM: To verify whether extra uterine changes in total peripheral vascular resistance and cardiac output, caused by raised haematocrit, occur in fetal life and if they can be documented using conventional ultrasound techniques. METHODS: An exchange transfusion with packed red cells was performed on five fetal lambs at 140 days of gestation (weight 3.44, SD 0.48 kg); three others were used as controls. The haematocrit was raised from 44 +/- 3 to 64 (SD2)%. RESULTS: Body temperature, blood gas, and pH remained within normal limits. Blood viscosity increased from 5.3 (0.3) to 9.6 (1.6) cps. Combined cardiac output fell to 30% of its initial value. The pulsatility index (PI) remained unchanged in the umbilical artery (0.66, SD 0.1) and descending aorta (1.3, SD 0.3). A significant positive correlation was found between haematocrit and PI only in the carotid artery (r = 0.67, p < 0.01). CONCLUSION: In the fetus, as in adults, an increase in blood viscosity is associated with a fall in cardiac output. However, the low resistance and the relative inertia of the placental vascular bed blunt the velocimetric changes that could be induced in the lower body vascular system by an increase in resistance. Such changes were observed only in the carotid artery. These results could be of interest in the Doppler monitoring of human fetuses at risk of an abnormal increase in their haematocrit.

Assessment of fetal pulmonic stenosis by ultrasonography.

This study was designed to determine (1) the value of Doppler echocardiography in depicting the presence of a fetal pulmonary stenosis, (2) its reliability in the assessment of the severity of the lesion, and (3) the usefulness of additional markers from the left side of the heart as criteria of severity. Fourteen pregnant ewes were included in this study (gestational age, 90 to 120 days). Banding of the fetal main pulmonary artery created mild (n = 3), moderate (n = 3), and severe (n = 5) stenosis. Three lambs were sham operated. Intrauterine fetal Doppler echocardiographic data obtained 15 days after surgery were compared with preoperative values. Peak velocities recorded through the band increased linearly from baseline in the groups with mild and moderate stenosis but did not show any further increase in the group with severe stenosis. Compared with the sham-operated group, right ventricular output in the group with stenosis was either similar or reduced significantly. The increase in right ventricular free wall thickness was significantly greater in the groups with stenosis compared with that of the sham-operated group; the correlation with the degree of severity was r = 0.65 and p < 0.05. A A stronger positive correlation was found between the severity of stenosis and aortic valve diameters: r = 0.82 and p < 0.01. The strongest correlation was found for right ventricular/left ventricular outputs (r = 0.92; p < 0.001). Thus Doppler peak velocities through the obstruction can help detect pulmonic stenosis but are not reliable for the assessment of its severity during fetal life. Other ultrasound measurements such as the size of the aortic anulus and especially the ratio of right ventricular/left ventricular output could be used as sensitive markers of the severity of stenosis.

Quantitative assessment of circulatory changes in the fetal aortic isthmus during progressive increase of resistance to umbilical blood flow.

BACKGROUND: This study investigated the effects of impairment to placental flow on flow patterns through the aortic isthmus because in the fetus, this vascular segment is the link between the parallel vascular systems perfused by the left and right ventricles. METHODS AND RESULTS: A progressive increase in resistance to blood flow through the placenta was created in seven exteriorized fetal lambs by mechanical umbilical vein compression. Blood flows were measured in the ascending aorta, pulmonary artery, aortic isthmus, and umbilical artery at baseline and at each compression level. The severity of the levels of compression was determined by changes in the flow profile through the umbilical artery. An increase in placental resistance causing a fall in umbilical blood flow of approximately 50% was associated with a retrograde diastolic flow through the aortic isthmus even though the diastolic flow through the umbilical artery remained forward. Because of the systolic predominance, however, the net flow in the isthmus was forward. With a more severe increase in placental resistance corresponding to a decrease of 75% in umbilical blood flow, the net flow through the isthmus approached zero. A strong positive correlation was found between the umbilical blood flow and the net flow through the aortic isthmus (r = .89). CONCLUSIONS: Variations in Doppler blood flow velocity waveforms and integrals of the aortic isthmus can be used as a sensitive indicator of the state of the umbilical circulation.

Reference values for Doppler velocimetric indices from the fetal and placental ends of the umbilical artery during normal pregnancy.

A range-gated Doppler ultrasound system combined with a real-time imaging system was used to determine arterial blood velocity values from the fetal and placental ends of the umbilical cord in 269 normal pregnancies between 17 and 40 weeks, menstrual age. The systolic-diastolic ratio (S/D), pulsatility index (PI), and resistance index (RI) were higher at the fetal end compared to the placental end of the cord. The individual differences in these Doppler indices, obtained between the fetal and placental recording sites, were inversely related to menstrual age: S/D: r = -0.38, p < 0.001; PI: r = -0.25, p < 0.001; and RI: r = -0.15, p < 0.01. After normalization for the angle of insonation, the peak systolic velocity was higher and the end-diastolic velocity was lower at the fetal than at the placental end of the cord. It is concluded that routine recordings for Doppler velocimetric indices should take into account the recording site on the umbilical cord in order to reduce methodological sources of variance, especially during midgestation. Furthermore, the data presented here in the form of the median and percentile values are proposed as normal reference values to facilitate this procedure.

Does unexplained second-trimester (15 to 20 weeks' gestation) maternal serum alpha-fetoprotein elevation presage adverse perinatal outcome? Pitfalls and preliminary studies with late second- and third-trimester maternal serum alpha-fetoprotein.

Several reports have suggested that persons with an unexplained maternal serum alpha-fetoprotein elevation at 15 to 20 weeks' gestation are at an increased risk for a variety of other pregnancy complications (e.g., preeclampsia) and adverse perinatal outcomes (e.g., fetal death, low-birth-weight infants). However, ascertainment biases could explain some of these reported findings, and predictive value of unexplained elevated maternal serum alpha-fetoprotein levels in the prediction of pregnancy complications seems limited. If elevated second-trimester levels were truly predictive of pregnancy complications, we reason that third-trimester levels could prove even more useful. We thus studied late second-trimester and early third-trimester (24 to 36 weeks' gestation) maternal serum alpha-fetoprotein levels with the same enzyme immunoassay we use to evaluate routine second-trimester (15 to 20 weeks' gestation) levels. Values rose up to 32 weeks and fell slightly thereafter. Variance was greater than at 15 to 20 weeks but not so great as to preclude clinical usefulness in the third trimester. Of 279 women with a normal (0.4 to 2.49 multiples of the median) maternal serum alpha-fetoprotein value at 15 to 20 weeks' gestation, 270 (96.8%) showed levels in the same range later in gestation; however, none of six singleton pregnancies with unexplained maternal serum alpha-fetoprotein levels greater than 2.50 multiples of the median at 15 to 20 weeks' gestation showed maternal serum alpha-fetoprotein levels in this range at 24 to 36 weeks' gestation. The relationship between second- and third-trimester maternal serum alpha-fetoprotein levels in abnormal pregnancies remains to be elucidated in a large sample. Thus we are conducting not only cohort but also cross-sectional studies. Preliminary findings suggest that women with preterm premature rupture of membranes or with premature labor show elevated late second-trimester and early third-trimester maternal serum alpha-fetoprotein levels; however, larger sample sizes are necessary.

The incidence of significant fetomaternal hemorrhage in patients undergoing cesarean section.

To determine the incidence of fetomaternal hemorrhage in patients undergoing cesarean section, Kleihauer-Betke tests were performed in the immediate postoperative period on 199 parturients. Some degree of hemorrhage was detected in 18.5% of patients, with 2.5% demonstrating greater than 30 ml of fetal blood. Comparison of groups on the basis of indication for cesarean delivery revealed no difference in rates of fetal hemorrhage. Because patients with greater than 30 ml of fetal blood would not be adequately protected from Rh sensitization by the standard 300 micrograms dose of Rh immune globulin, we recommend screening all Rh-negative patients undergoing cesarean section for the presence of significant fetomaternal hemorrhage.