Detection of severe congenital heart defects in live-born infants in Norway 2017-2020.

AIM: The aims of this nationwide retrospective cohort study were to determine the time and causes of detection of severe congenital heart defects (CHDs) in live-born infants in Norway between 2017 and 2020. METHODS: Information regarding live-born infants with severe CHDs was retrieved from national registries and medical records. RESULTS: A total of 219 776 infants were born in Norway from 01.01.2017 to 31.12.2020. Severe CHDs were diagnosed in 442 (0.2%) infants. Of these, 376 (85%) infants were diagnosed either prenatally (n = 203, 46%) or before discharge from hospital after birth (n = 173, 39%). A total of 56 (13%) infants were discharged with undetected CHDs. Time of detection was unknown in 10 cases (2%). The most frequent undetected CHDs at discharge were coarctation of the aorta/aortic arch hypoplasia (n = 24), atrioventricular septal defect (n = 13), anomalous pulmonary venous connection (n = 5) and coronary artery anomalies (n = 4). Seven (13%) children with undetected CHD experienced circulatory collapse out of hospital. CONCLUSION: Most infants with severe CHDs in Norway were identified prior to hospital discharge. However, some infants were discharged undiagnosed. Awareness of undetected CHDs and immediate cardiac assessment in infants with signs of circulatory failure early in life are still important.

Controversies in implementing non-invasive prenatal testing in a public antenatal care program.

Women's autonomy and an inclusive society for all individuals are highly valued in Norway. The Norwegian Biotechnology Act changed in 2020 allowing first-trimester screening and cell-free DNA for common trisomies to all pregnant women. However, implementing non-invasive prenatal testing (NIPT) in a public antenatal care program is difficult, because many patients, politicians, and medical professionals do not consider trisomy 21 a severe medical disease. Screening for trisomies at an early gestation might inevitably lead to an increase in pregnancy terminations and making cost-benefit calculations is ethically challenging. Moreover, offering NIPT to all pregnant women is debatable because of the lower prevalence of fetal trisomies in younger women. Therefore, appropriate genetic pre-test counseling is essential. Furthermore, organizing the service between private institutions and public hospitals poses another debate and challenges both quality and equal access to health services for women across the country.

Platelet alloimmunization is associated with low grade chronic histiocytic intervillositis - A new link to a rare placental lesion?

INTRODUCTION: Maternal alloimmunization against human platelet antigen (HPA)-1a has been implied to mediate both reduced birth weight and chronic placental inflammation. Fetal growth restriction is associated with different types of chronic inflammation in the placenta, mainly chronic histiocytic intervillositis and chronic villitis. The aim of this prospective study was to do a systematic examination of placentas from HPA-1a alloimmunized pregnancies, with focus on the histopathological and immunohistochemical diagnosis of variants of chronic inflammation. MATERIAL AND METHODS: In a Polish-Norwegian study, 48 placentas were examined. The histopathology of placentas from 27 HPA-1a immunized women was compared with 21 placentas from non-immunized HPA-1a negative women (controls). In the group of alloimmunized women, ten received antenatal intravenous immunoglobulin G (IVIg). Tissue sections from formalin fixed paraffin embedded placental tissue were stained with hematoxylin and eosin and microscopically examined with focus on various types of chronic placental inflammations. RESULTS: Chronic histiocytic intervillositis was observed in 40.7% of placentas from HPA-1a alloimmunized pregnancies, compared to none in the control group (p = 0.001). Chronic villitis of unknown etiology was more frequently found in the alloimmunized group, however this difference was not statistically significant. Maternal administration of IVIg did not seem to protect against chronic inflammatory lesions. DISCUSSION: Placentas with detectable maternal anti-HPA-1a antibodies are associated with highly increased risk of low-grade chronic histiocytic intervillositis.

Pregnant women's attitudes to prenatal screening in Norway. / Gravide kvinners holdning til fosterdiagnostikk.

BACKGROUND: Prenatal screening in Norway is governed by the Biotechnology Act. According to the Act, which was adopted in 2003, prenatal screening in early pregnancy may only be offered to women with an elevated risk of having a child with chromosomal abnormalities or malformations. This type of prenatal screening is undertaken at fetal medicine centres. The purpose of this study was to identify attitudes to prenatal screening among pregnant women in the Oslo region. MATERIAL AND METHOD: In the period August-November 2019, we distributed a questionnaire to all pregnant women who attended for routine ultrasound examination at Oslo University Hospital (Rikshospitalet and Ullevål hospitals) and Akershus University Hospital. Factors characterising women with different attitudes were identified. RESULTS: We invited 1 212 women, 1 170 (96.5 %) of whom responded to the questionnaire survey. Of the 1 159 who answered the relevant question, 909 (78.4 %) believed that prenatal screening should be offered by the public health service to all pregnant women, and 882 of 1 026 (86 %) had paid for a private ultrasound examination early in their pregnancy. Of 690 who were aware of the non-invasive prenatal test (NIPT), 190 (27.5 %) had paid for the test. Place of birth, education, religion and parity were factors that differentiated women with different attitudes to prenatal screening. INTERPRETATION: The majority of pregnant women in the Oslo region wanted to be offered early prenatal screening. Sociodemographic characteristics were a decisive factor with regard to women's attitudes to a prenatal screening service.

A young woman with a transfusion-related pregnancy complication. / En ung kvinne med transfusjonsutløst svangerskapskomplikasjon.

BACKGROUND: Individuals with the K0 phenotype are extremely rare. They may develop anti-Ku antibodies, which react with all antigens of the Kell blood group system, thereby leading to haemolytic transfusion reactions and haemolytic disease of the fetus and newborn. CASE PRESENTATION: A primigravida who was transfused with one unit of red blood cells due to iron deficiency anaemia developed anti-Ku antibodies. The pregnancy was closely monitored by ultrasound and antibody titres. Maternal autologous blood collection was performed twice during the last trimester as back-up in case of maternal peripartum bleeding, and a few frozen K0 red blood cell units were provided in case of severe fetal anaemia. At gestational week 36+6, labour was induced due to increasing antibody titres and high blood velocities in the fetal middle cerebral artery during systole. The woman was delivered vaginally without need for transfusion. The infant was diagnosed with haemolytic disease of the fetus and newborn and treated with phototherapy, repeated infusions of intravenous immunoglobulin and iron supplements until normalisation of haemoglobin at three months of age. INTERPRETATION: Iron deficiency anaemia should be treated primarily with iron supplementation before considering blood transfusions, which pose the risk of developing alloantibodies that can cause transfusion complications and haemolytic disease of the fetus and newborn.

Diagnosis of severe congenital heart defects in Norway 2016. / Diagnostikk av alvorlige medfødte hjertefeil i Norge 2016.

BACKGROUND: Most structural congenital heart defects can be identified prenatally through ultrasound examination in pregnancy or via routine examinations during hospital maternity stays, but in some cases, heart defects are not discovered prior to discharge. There has been little previous research into detection rates with the various methods available. In this study, we have examined the timing and method of diagnosis of severe congenital heart defects. MATERIAL AND METHOD: All children with severe heart defects born in Norway in 2016 and registered at Oslo University Hospital were included in this study. In addition, information on committee-handled abortions (after the 12th week of pregnancy) was obtained from the Medical Birth Registry of Norway. RESULTS: In total, 105 of 181 (58 %) severe heart defects were diagnosed prenatally, and 51 (28 %) pregnancies were terminated. Among the 73 live-born children with severe heart defects that went unrecognised prenatally, 33 (45 %) of the heart defects were discovered outside of routine examinations and 9 (12 %) after discharge from hospital. Coarctation of the aorta was the most common diagnosis in cases of late-detected heart defects. INTERPRETATION: This first national study of the diagnosis of severe congenital heart defects in Norway shows that most severe congenital heart defects are discovered prior to discharge from hospital after birth. However, almost half are diagnosed outside of routine examinations, and in some cases the diagnosis is not made until after discharge. The results indicate a need for new studies and for a quality registry of congenital heart defects to further improve diagnosis and early treatment.

Laeverin protein expression in normal and preeclamptic placentas using tissue microarray analysis.

INTRODUCTION: Laeverin is a placenta-specific protein that is normally expressed in the plasma membrane of human trophoblasts. In previous studies, we showed higher expression levels of laeverin gene in preeclamptic compared with normal placentas and found that laeverin protein was ectopically expressed in the cytoplasm of the preeclamptic placentas. Our objective was to investigate laeverin protein expression in normal and preeclamptic placentas combining immunohistochemistry and immunofluorescence. MATERIAL AND METHODS: Tissue microarray analysis of 72 placentas, obtained from 33 preeclamptic and 39 uncomplicated pregnancies, was performed. Laeverin was labeled with a specific antibody for immunohistochemistry and immunofluorescence studies. RESULTS: Immunohistochemistry showed that laeverin was expressed in syncytiotrophoblasts, cytotrophoblasts and extravillous trophoblasts in all placentas examined. In preeclamptic placentas (n = 33) compared with normal placentas (n = 39), laeverin was expressed in the cell membrane in 21 (64%) vs. 21 (54%) samples (p = 0.726), in the cytoplasm in 3 (9%) vs. 2 (5%) samples (p = 0.795) and in both the cytoplasm and membrane in 9 (27%) vs. 16 (41%) samples (p = 0.0522). All placental samples that showed cytoplasmic expression of laeverin were obtained from women who delivered before 34 weeks of gestation (early-onset preeclampsia). Further, immunofluorescence studies showed laeverin expression in the cytoplasm of six preeclamptic (three early-onset and three late-onset) and one normal placenta but did not reveal any simultaneous cell membrane and cytoplasmic expression of laeverin. CONCLUSION: Laeverin is expressed in all trophoblast cell types of normal and preeclamptic placentas. Expression pattern of laeverin in trophoblast cells is heterogeneous and not necessarily membrane-bound.

Obstetric and psychological characteristics of women choosing epidural analgesia during labour: A cohort study.

OBJECTIVES: To investigate the obstetric and psychological characteristics of women who opt to use epidural analgesia (EDA) during labour and the impact of participating in labour preparation courses on women's decisions to use EDA. DESIGN: Longitudinal cohort study. SETTING: Akershus University Hospital, Norway. POPULATION: 2596 women with singleton pregnancies and intended vaginal delivery. METHODS: Data were collected using two self-completed questionnaires at pregnancy weeks 17 and 32. Fear of childbirth was assessed by the Wijma Delivery Expectancy Questionnaire (W-DEQ). Symptoms of anxiety were measured by the Hopkins Symptom Check List (SCL-25) and depression by the Edinburgh Postnatal Depression Scale (EPDS). Obstetric and socio-demographic information was retrieved from birth records at the maternity ward. MAIN OUTCOME MEASURE: Preference for EDA was indicated by the questionnaire item "I would prefer an epidural regardless" on a 4-point scale (1 = highly agree, 4 = highly disagree) at pregnancy week 32. RESULTS: Twenty-one percent of the women (540/2596) answered that they would choose EDA as the only alternative method of analgesia during labour. Counselling for fear of childbirth [OR 3.23 (95%CI 2.12; 4.92)] and W-DEQ sum score ≥ 85 [OR 2.95 (95%CI 2.06; 4.23)] were significantly (p<0.001) associated with choice of EDA. Participation in labour preparation courses was significantly (p = 0.008) associated with a reduction of intended use of EDA during labour [OR 0.67 (95%CI 0.49; 0.90)]. CONCLUSION: Fear of childbirth is significantly associated with women's choice of EDA during labour. On the other hand, women that participate in labour preparation courses would rather consider other methods of analgesia during labour.

Longitudinal reference ranges for maternal plasma laeverin, and its role as a potential biomarker of preeclampsia.

BACKGROUND: Laeverin is a placenta-specific membrane-bound aminopeptidase. In this study we wanted to: 1) serially measure plasma levels of laeverin in healthy women during the second half of pregnancy and postpartum, 2) determine whether laeverin is differently expressed at 22-24 weeks in women who later develop preeclampsia compared to controls, 3) compare laeverin protein expression in placenta and umbilical vein serum in healthy and preeclamptic pregnancies at birth. METHODS: Plasma was obtained serially, approximately every 4-weeks, from 53 healthy women with uncomplicated pregnancies during 22+0 to 39+6 weeks of gestation, and at 22-24 weeks from 15 women who later developed preeclampsia. Enzyme-linked immunosorbent assay was used to measure laeverin protein concentration. Serum from healthy non-pregnant premenopausal women (n = 10), menopausal women (n = 10) and men (n = 11) were used as negative controls. Protein extracts from placental tissue were obtained after birth from healthy- (n = 11) and preeclamptic women (n = 13). Paired umbilical artery and vein serum samples from the neonates (n = 10) of healthy mothers were also analyzed. Multilevel modeling was used to determine the reference centiles. Differences between groups were analyzed using Student's t-test. RESULTS: Healthy pregnant women at term (37-40 weeks) had significantly higher plasma levels of laeverin (mean 4.95 ± 0.32 ng/mL; p < 0.0001) compared to men (mean 0.18 ± 0.31 ng/mL), non-pregnant premenopausal women (mean 0.77 ± 0.26 ng/mL) and postmenopausal women (mean 0.57 ± 0.40 ng/mL). Maternal plasma laeverin levels decreased with advancing gestation, from 6.96 ± 0.32 ng/mL at 22-24 weeks to 4.95 ± 0.32 ng/mL at term (p < 0.0001) in uncomplicated pregnancies. Half of the women who developed preeclampsia had plasma laeverin levels below the 5th percentile at 22-24 weeks gestation. However, laeverin levels were 1.6 fold higher in preeclamptic compared to healthy placentas (p = 0.0071). Umbilical venous samples of healthy neonates (n = 38) had higher (p = 0.001) mean levels of laeverin (16.63 ± 0.73 ng/mL), compared to neonates of preeclamptic (n = 14) mothers (12.02 ± 1.00 ng/mL). Postpartum plasma levels of laeverin decreased in healthy and preeclamptic women with a half-life of 3 and 5 days, respectively. CONCLUSIONS: Maternal plasma levels of laeverin decrease with advancing gestation during the second half of normal pregnancy and lower levels measured at 22-24 weeks might be associated with the development of preeclampsia later in gestation.

Towards a new era in fetal medicine in the Nordic countries.

Fetal medicine is a subspecialty of obstetrics investigating the development, growth and disease of the human fetus. The advances in fetal imaging (ultrasonography, MRI) and molecular diagnostic techniques, together with the possibility of intervention in utero, make fetal medicine an important, rapidly developing field within women's healthcare. Therefore, a variety of specialists, such as neonatologists, pediatric cardiologists, medical geneticists, radiologists and pediatric surgeons, are necessary to adjunct in the diagnosis and treatment of the fetus as a patient. In this commentary, we provide a description of some organizational and educational aspects of fetal medicine in the Nordic countries, using examples of the management of specific conditions such as aneuploidy screening, red cell allo-immunization and fetal interventions. Clearly, there are several cultural, legal, organizational and practical differences between the Nordic countries; these are not necessarily negative, given the high standards of care in all Nordic countries. The scope of the newly founded Nordic Network of Fetal Medicine is to enhance cooperation in clinical practice, education and research between the participant countries. Hopefully, this initiative will find the necessary political and economic support from the national authorities and bring a new era in the field of fetal medicine in the Nordic region.

Coronary flow reserve in pregnant rats with increased left ventricular afterload.

BACKGROUND: Coronary flow reserve (CFR) is used as a measure of coronary endothelial function. We investigated the effect of increased afterload on CFR of pregnant and non-pregnant rats. METHODS: Afterload increase in Wister rats (both pregnant and non-pregnant) was achieved by the infusion of angiotensin II (Ang II) for ∼10 days or by subjecting them to transverse aortic constriction (TAC) for ∼14 days. Control groups were infused with 0.9% NaCl or had sham surgery, respectively. In pregnant rats, the experiments were performed close to term gestation. Doppler velocity waveforms of the left main coronary artery were recorded using a high resolution ultrasound imaging system (Vevo 770, VisualSonics, Canada) at baseline while the animals were anesthetized with 1.5% inhaled isoflurane, and during maximal coronary dilatation obtained by the inhalation of 3.5% of isoflurane. CFR was calculated as the ratio between the peak coronary flow velocities (CFRpeak) and the velocity-time integrals (CFRVTI) recorded at hyperemia and at baseline. RESULTS: CFR could be calculated in 60 of 75 (80%) animals. There were no differences in CFR between intervention and control groups irrespective of whether afterload was increased by Ang II or TAC. In the TAC-study CFRpeak (1.54±0.07 vs 1.85±0.17; p = 0.03) was decreased in pregnant compared to non-pregnant shams. When sham animals from both studies were pooled together both CFRpeak (1.42±0.07 vs 1.86±0.16; p = 0.005) as well as CFRVTI (1.45±0.07 vs 1.78±0.12; p = 0.03) were significantly lower in pregnant rats compared to non-pregnant. CONCLUSIONS: CFR can be measured non-invasively in rats using Doppler echocardiography and high concentrations of inhaled isoflurane as a coronary vasodilator. In pregnant rats, CFR is reduced close to term. CFR is not affected by increased left ventricular afterload caused by chronic Ang II infusion or TAC.

Placental expression of aminopeptidase-Q (laeverin) and its role in the pathophysiology of preeclampsia.

OBJECTIVE: The purpose of this study was to investigate the expression and subcellular localization of laeverin, a placenta-specific membrane-bound aminopeptidase, in preeclamptic placentas and its role in trophoblast cell migration and invasion. STUDY DESIGN: Expression of laeverin was investigated in 6 normal and 6 preeclamptic placentas with the use of immunofluorescence, sodium dodecylsulfate-polyacrylamide gel electrophoresis with Western blot analysis and immunoelectron microscopy. The role of laeverin in trophoblast migration and invasion was studied with the use of the xCelligence system and Boyden chambers with Matrigel in HTR-8/SVneo cells. The effect of laeverin gene-silencing on selected genes that are involved in cell transformation and tumorigenesis was evaluated by polymerase chain reaction array. The Student t test, Mann-Whitney U test, χ(2) test, or F-test was used to compare groups as appropriate. RESULTS: Laeverin was expressed in the cell membrane of villous trophoblasts in third-trimester healthy placentas; in preeclamptic placentas, it was expressed ectopically in the cytoplasm, especially in microvesicles. Immunoelectron microscopy showed laeverin leakage into the fetal capillaries and abundant expression in microvesicles in preeclamptic placentas. Migration and invasion of HTR-8/SVneo cells were reduced by 11.5% (P = .023) and 56.7% (P = .001), respectively, by laeverin gene-silencing. Analysis of downstream pathways affected by laeverin-silencing demonstrated significant down-regulation of integrin A2 (39-fold), integrin B3 (5-fold), and matrix metalloprotease 1 (36-fold). CONCLUSION: Expression of laeverin protein is altered in preeclamptic placentas. Its ectopic expression in the cytoplasm and microvesicles, rather than the cell membrane and leakage into the fetal capillaries, may have a role in the pathophysiologic condition of preeclampsia. Laeverin gene appears to be involved in trophoblast cell migration and invasion through interaction with integrins and matrix metalloprotease 1.

PP030. Transmission electron microscopy reveals leakage of laeverin into the villous capillaries and ectopic expression in the cytoplasm instead of cell membrane of the trophoblasts in preeclamptic placentas.

INTRODUCTION: Laeverin, a membrane-bound aminopeptidase is specifically expressed in human placenta. We previously reported that mRNA levels of laeverin-gene are up-regulated in the placentas of severely preeclamptic women compared to healthy controls. Furthermore, immunofluorescence studies indicated that laeverin is expressed in the cytoplasm rather than the cell membrane of preeclamptic placentas. OBJECTIVE: To study differences in size and integrity of laeverin protein expressed in preeclamptic and normal placentas, and to investigate sub-cellular localization of laeverin, in the trophoblasts. METHODS: Proteins from placental tissue of three severely preeclamptic women and three healthy controls were extracted using Magnabeads in MagNaLyser in T-PER solution. Western blot analysis was done by SDS-polyacrylamide gel electrophoresis and electro-blotting on PVDP membranes. Membranes were developed by Tropix CDP-Star and immuno-reactive bands were visualised. Immuno-electronmicroscopy was performed on high pressure freezed (Tokyasu method) tissue samples of three placentas (from1 healthy and 2 severely preeclamptic women). Ultrathin sections were fixed and labeled with primary antibody raised against laeverin, followed by antibody conjugated with 5nm gold particles (PAG5). Experiments were performed in triplicates and images were taken using a JEM-1010 transmission electron microscope at 50,000 and 70,000 magnifications. RESULTS: Western blot analysis detected laeverin-protein of normal size (approximately 100kDa) both in normal and preeclamptic placentas. However, laeverin was overexpressed in preeclamptic placentas compared to healthy controls. Immuno-electronmicroscopy revealed presence of laeverin within the capillaries in preeclamptic placentas which was not seen in healthy controls. At a sub-cellular level laeverin was localized on the cell membrane of trophoblasts in healthy placentas. However, in preeclamptic placentas, laeverin was localized in the cytoplasm and in particular in the Golgi apparatus. CONCLUSIONS: In preeclamptic placentas, laeverin is overexpressed and it appears to leak into the villous capillaries and localize in the cytoplasm instead of cell membrane of the trophoblasts.

Differences in gene expression between first and third trimester human placenta: a microarray study.

BACKGROUND: The human placenta is a rapidly developing organ that undergoes structural and functional changes throughout the pregnancy. Our objectives were to investigate the differences in global gene expression profile, the expression of imprinted genes and the effect of smoking in first and third trimester normal human placentas. MATERIALS AND METHODS: Placental samples were collected from 21 women with uncomplicated pregnancies delivered at term and 16 healthy women undergoing termination of pregnancy at 9-12 weeks gestation. Placental gene expression profile was evaluated by Human Genome Survey Microarray v.2.0 (Applied Biosystems) and real-time polymerase chain reaction. RESULTS: Almost 25% of the genes spotted on the array (n = 7519) were differentially expressed between first and third trimester placentas. Genes regulating biological processes involved in cell proliferation, cell differentiation and angiogenesis were up-regulated in the first trimester; whereas cell surface receptor mediated signal transduction, G-protein mediated signalling, ion transport, neuronal activities and chemosensory perception were up-regulated in the third trimester. Pathway analysis showed that brain and placenta might share common developmental routes. Principal component analysis based on the expression of 17 imprinted genes showed a clear separation of first and third trimester placentas, indicating that epigenetic modifications occur throughout pregnancy. In smokers, a set of genes encoding oxidoreductases were differentially expressed in both trimesters. CONCLUSIONS: Differences in global gene expression profile between first and third trimester human placenta reflect temporal changes in placental structure and function. Epigenetic rearrangements in the human placenta seem to occur across gestation, indicating the importance of environmental influence in the developing feto-placental unit.

Cardiopulmonary Collapse during Labour.

Cardiopulmonary collapse during labour is a catastrophic event caused by various medical, surgical and obstetrical conditions. It is an emergency that threatens the life of the mother and her unborn child. We present a case of a pregnant woman who suffered from preeclampsia and underwent induction of labour. Severe lung edema occurred early in labour that caused cardiopulmonary collapse. Advanced heart-lung resuscitation was established immediately and continued until an emergency cesarean section was performed few minutes later. The outcome was favourable for both mother and child. We further discuss some aspects of the pathophysiology and appropriate treatment of cardiorespiratory arrest during labour, which involves the coordinated action of the obstetric, pediatric and surgical ward personnel.

Placental gene expression profile in intrauterine growth restriction due to placental insufficiency.

We evaluated global placental gene expression in intrauterine growth restriction (IUGR; n = 8) compared to normal pregnancies (n = 8) and studied possible additional effect of preeclampsia. Placental samples were collected from IUGR pregnancies due to placental insufficiency ascertained by hemodynamic studies. Four IUGR pregnancies were associated with preeclampsia. Gene expression profile was evaluated by 30k oligonucleotide microarrays. Principal component analysis (PCA) showed good separation in terms of gene expression patterns between the groups. Pathway analysis showed upregulation of inflammation mediated by chemokine and cytokine signaling pathway in the IUGR placentas. Genes involved in placental glucocorticoid metabolism were also differentially expressed. None of the known imprinted placental genes were differentially expressed. Subgroup analysis between IUGR placentas with and without preeclampsia showed few (n = 27) differentially expressed genes. In conclusion, IUGR due to placental insufficiency appears to alter placental glucocorticoid metabolism, upregulates inflammatory response in placenta, and shares common pathogenic mechanisms with severe early-onset preeclampsia.

Oxygen uptake of the human fetus at term.

OBJECTIVE: To measure oxygen uptake of term human fetuses and compare the values between those delivered vaginally following normal labor and those delivered by cesarean section before the onset of labor. DESIGN: This was a prospective cross-sectional study. SETTING: University teaching hospital. SAMPLE: Twenty healthy pregnant women at term (38-42 weeks) were included in this study. Among them, 10 were delivered by elective cesarean section and 10 had normal vaginal delivery. METHODS: Umbilical vein volume blood flow was measured <24 hours before delivery. Immediately after delivery, the fetal weight was determined, and the umbilical venous and arterial blood samples were obtained. Blood gas analysis was performed and hemoglobin content was measured. Fetal oxygen uptake was calculated as a product of umbilical venous blood flow and the difference in the umbilical arterial and venous oxygen content. RESULTS: We found that the mean oxygen uptake in human fetuses at term (median gestational age 39 weeks) to be 6.58 ml/min/kg (i.e. 0.29 mmol/min/kg). There was no significant difference in oxygen uptake between fetuses delivered following uncomplicated normal labor and those delivered by elective cesarean section before the onset of labor. CONCLUSION: Oxygen uptake of the appropriately grown normal human fetus at term is approximately 6.6 ml/kg/min and is not significantly affected by normal labor and delivery. Human fetuses tolerate intermittent reductions in uterine blood flow and oxygen supply associated with myometrial contractions during normal labor quite well.