Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

The predictive value of the sFlt-1/PlGF ratio in suspected preeclampsia in a New Zealand population: A prospective cohort study.

BACKGROUND: Internationally, placental growth factor (PlGF)-based tests are used as prognostic markers in suspected preeclampsia. However, Ministry of Health guidelines do not currently endorse PlGF-based tests in New Zealand (NZ). AIMS: To investigate the predictive value of soluble fms-like tyrosine kinase 1 (sFlt-1)/PlGF ratio in suspected preeclampsia in a NZ population. MATERIALS AND METHODS: A prospective cohort study of singleton pregnancies at 20+0 -36+6 weeks gestation with suspected preeclampsia as defined by Society of Obstetric Medicine Australia and NZ (SOMANZ) criteria. PRIMARY OBJECTIVE: to evaluate a sFlt-1/PlGF ratio >38 at ≤35+0 weeks gestation to predict birth ≤14 days. SECONDARY OBJECTIVES: to assess a sFlt-1/PlGF ratio cut-off of 38 at ≤37+0 weeks gestation, to rule out preeclampsia ≤1 week, rule in preeclampsia ≤4 weeks, and to predict perinatal outcome. Clinicians were blinded to sFlt-1/PlGF ratio results. RESULTS: Included were 222 participants, 19.4% Maori and 10.4% Pasifika. A sFlt-1/PlGF >38 predicted birth ≤14 days, positive predictive value (PPV) 51.4% (95% CI, 39.6-63.0) and negative predictive value (NPV) 95.9% (95% CI, 91.4-98.1), median (interquartile range) days to birth 14 (2-27) vs 49 (33-70), P < 0.000. A sFlt-1/PlGF cut-off of 38 ruled out preeclampsia ≤1 week (NPV 96.2% (95% CI, 92.3-98.2)) and ruled in preeclampsia ≤4 weeks (PPV 75.0% (95% CI, 65.0-82.9)). A sFlt-1/PlGF >38 was associated with greater perinatal morbidity. CONCLUSIONS: The predictive value of the sFlt-1/PlGF ratio in NZ is comparable to that reported in international trials. Used in clinical practice the sFlt-1/PlGF ratio may aid risk stratification in suspected preeclampsia, directing limited resources to those pregnancies at highest risk.

Opposition to abortion related to inaccurate beliefs about fetal pain perception in utero.

BACKGROUND: Misinformation about abortion and pregnancy is common. Restrictions on abortion access at and beyond 20 weeks are frequently justified using the claim that a fetus can experience pain before the third trimester. The current medical consensus is that it is unlikely that fetal pain perception is possible before the 29th or 30th weeks of pregnancy. AIMS: To examine the relationship between abortion attitudes and beliefs about when a fetus develops the capacity to perceive pain in utero. METHODS AND MATERIALS: We used Amazon's Mechanical Turk to recruit participants residing in the United States (N = 374) and used an online questionnaire to assess their beliefs about abortion and the ability of a fetus to perceive pain. RESULTS: Anti-choice participants were more likely than pro-choice participants to believe that a fetus in utero can perceive pain before the 23rd week of pregnancy (63.4 vs. 48.5%, P = 0.010) and in the first trimester (40.1 vs. 15.8%, P < 0.000). Most Black and Catholic participants, along with those with advanced degrees, believed that fetal pain is not possible before the third trimester. CONCLUSIONS: Most participants believed that a fetus develops the capacity to perceive pain earlier than developmental reality, and this belief correlates with anti-choice views.

Pregnant women's knowledge of, and adherence to, New Zealand Food Safety in Pregnancy guidelines.

AIM: Pregnant women are at increased risk for contracting foodborne illness. Simple food safety precautions can prevent illness. The aim of this study was to examine pregnant women's knowledge of, and adherence to, the New Zealand Food Safety in Pregnancy guidelines. METHOD: Participants were recruited when attending antenatal clinics, and via online pregnancy support groups. Knowledge and behaviours were assessed by way of a self-administered questionnaire. RESULTS: In total, 205 women participated in this study; 100 from antenatal clinics, 105 via Facebook. The median knowledge score was 95% (interquartile range (IQR) 83-100%, minimum = 17.4%). Only 25% of participants answered all questions correctly. The median adherence score was 77% (IQR = 62-92%, minimum = 8%); 13% of participants reported complete adherence to the food safety guidelines. Mean knowledge scores in participants of Maori ethnicity (76.6%) were lower than in participants of European/other ethnicity (91.7%, p=0.004). Maori participants had the lowest mean adherence scores (63.2%) and this requires further investigation. CONCLUSIONS: The majority of participants reported continuing to consume foods considered unsafe in pregnancy. This study highlights the need for improved food safety education during pregnancy. The results also suggest a need for food safety guidance to be made more accessible and relevant to the needs of Maori women.

The epidemiology of listeriosis in pregnant women and children in New Zealand from 1997 to 2016: an observational study.

BACKGROUND: Listeria monocytogenes causes the foodborne infection listeriosis. Pregnant women, infants and immunocompromised children are at increased risk for infection. The aim of this study was to describe the trends in the epidemiology of disease notifications and hospital admissions due to listeriosis in pregnant women aged 15 to 45 years and children aged less than 15 years in New Zealand (NZ) from 1997 to 2016. METHODS: In this population-based descriptive study, listeriosis notification and hospitalization rates from 1997 to 2016 were analyzed. Notification data were extracted from the Institute of Environmental Science and Research (ESR) Notifiable Diseases Database (EpiSurv) and hospitalization data were extracted from the National Minimum Dataset (NMDS). Pregnant women aged 15 to 45 years and children less than 15 years of age were included. Subgroup analysis was conducted for age and ethnicity. Outcomes of infection were described. RESULTS: In the 20-year period considered, there were 147 pregnancy-associated cases of listeriosis either notified to ESR (n = 106) and/or coded in the NMDS (n = 99), giving a crude incidence rate of 12.3 (95% CI 10.4, 14.4) per 100,000 births. In addition, there were 22 cases in children aged 28 days to < 15 years (incidence =0.12, 95% CI 0.08 to 0.19 per 100,000). There were no trends observed over time in the incidence of pregnancy-associated listeriosis. Incidence rates of pregnancy-associated and childhood listeriosis were highest in people of Pacific and Asian ethnicity. CONCLUSIONS: NZ has a low incidence of listeriosis in pregnant women and children, however, the consequences of infection are frequently severe. Those of Pacific and Asian ethnicity have the highest rates of disease and future messaging around food safety should target these groups. This study provides important insights into the epidemiology of listeriosis in pregnant women and children in NZ.

The effect of a major earthquake experienced during the first trimester of pregnancy on the risk of preterm birth.

BACKGROUND: On 22 February 2011 an earthquake (magnitude 6.3) hit Christchurch, New Zealand. Earthquakes have been associated with increased risks of preterm birth (PTB) and other adverse pregnancy outcomes. However, the literature on this subject is scarce. Maternal antenatal stress has been suggested as the link between earthquakes and PTB. In this study the Christchurch earthquake was utilised as a model of maternal stress to assess its effects on PTB rates and other pregnancy outcomes. AIM: To investigate whether women who experienced a major earthquake during the first trimester of pregnancy were at an altered risk of PTB compared to women who did not experience an earthquake during their pregnancy. METHODS: This was a retrospective cohort study. Women carrying a singleton pregnancy in their first trimester on 22 February, 2011 were identified for a post-earthquake cohort (n = 1057). A group of women pregnant in 2009 were identified for a pre-earthquake cohort (n = 1314). Data were obtained from electronic medical records and the hospital clinical coding database. Chi-square test, Fisher's exact test and Wilcoxon rank sum test were used to analyse differences in pregnancy outcomes. Statistically significant variables together with earthquake exposure were assessed as risk factors for PTB using a multivariate logistic regression model. RESULTS: No significant difference in the rate of PTB was found between the two groups P > 0.05). CONCLUSION: Women carrying a singleton pregnancy in this study who experienced a major earthquake in their first trimester do not seem to be at an increased risk of PTB.

Evaluation of the NZ guidelines for screening for persistent postpartum hyperglycaemia following gestational diabetes.

BACKGROUND: Recent New Zealand guidelines recommend annual glycated haemoglobin (HbA1c) measurements from three months postpartum, replacing the glucose tolerance test (GTT) at six weeks, to screen for persistent hyperglycaemia following gestational diabetes. Data suggest that this screening approach may miss cases of type 2 diabetes, but are they detected at subsequent screening and will screening rates improve? AIMS: Our aim was to evaluate the effectiveness of HbA1c monitoring in improving screening rates following gestational diabetes and in detecting postpartum hyperglycaemia. MATERIALS AND METHODS: During 2015 in Christchurch, all women with gestational diabetes were offered HbA1c and GTT measurements at three months postpartum and subsequent annual HbA1c measurements were recommended. Data from electronic hospital records were collected for a minimum 18 months postpartum. RESULTS: Of the cohort of 333 women, 218 (65%) completed both HbA1c and GTT at three months postpartum, 74 (22%) HbA1c only, 16 (5%) GTT only, 25 (8%) no screening; 184 (55%) had subsequent HbA1c tests. Diabetes was detected by GTT in five (2%) women and by HbA1c in only one out of five (20%); the disagreement between tests resolved in three out of four (75%) women with subsequent testing. Prediabetes was detected by GTT in 30 (14%) women; however, HbA1c only detected five out of 30 (17%) and subsequent HbA1c testing identified a further two out of 30 with prediabetes. CONCLUSIONS: HbA1c measurement at three months postpartum had a good uptake. However, most cases of diabetes were identified by subsequent HbA1c testing, the uptake of which was suboptimal. The importance of annual HbA1c monitoring following gestational diabetes needs greater emphasis.

Antenatal haemoglobin A1c centiles: does one size fit all?

BACKGROUND: In New Zealand, haemoglobin A1c measurements are routinely offered at booking, preferably before 20 weeks gestation, to detect pre-existing hyperglycaemia. A haemoglobin A1c <5.9% (41 mmol/mol) is considered normal based on the reference range for the non-pregnant population. AIMS: To determine pregnancy-specific haemoglobin A1c centiles by gestation and ethnicity. MATERIALS AND METHODS: This is a population-based observational study of pregnancies uncomplicated by diabetes (pre-existing or gestational) with ≥1 haemoglobin A1c measurement. Haemoglobin A1c centiles were calculated from data extracted from electronic laboratory and clinical records for pregnancies during 2008-2010. RESULTS: Included were 6800 pregnancies, European 80% (5462), Maori 6% (415), Pacific Islander 3% (196) and 11% (727) 'Others' (mostly Asian). Haemoglobin A1c levels fell with increasing gestation, reaching a nadir at 24 weeks, a trend verified by longitudinal data from 112 women. The 97.5th centile for haemoglobin A1c in European women was 5.76% (39.5 mmol/mol) at 8+0  weeks, 5.70% (38.8 mmol/mol) at 16+0  weeks, and 5.65% (38.3 mmol/mol) at 24+0  weeks. Non-European women had both higher plasma glucose levels (although within the range considered normal) and higher mean haemoglobin A1c levels compared with Europeans; mean (SD) difference in haemoglobin A1c in Maori +0.13% (0.05) (+1.4 mmol/mol (0.5)), Pacific +0.20% (0.03) (+2.2 mmol/mol (0.3)), 'Others' +0.10% (0.03) (+1.1 mmol/mol (0.3)). CONCLUSIONS: The New Zealand haemoglobin A1c cut-point ≥5.9% (41 mmol/mol) for identifying hyperglycaemia in early pregnancy is greater than the 97.5th centile in European and 'Other' women. Utilising population haemoglobin A1c centiles adjusted by gestation may thus better guide management decisions.

Delayed versus Immediate Cord Clamping in Preterm Infants.

BACKGROUND: The preferred timing of umbilical-cord clamping in preterm infants is unclear. METHODS: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births. RESULTS: Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. CONCLUSIONS: Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .).

Pregnant women lack accurate knowledge of their BMI and recommended gestational weight gain.

AIM: To investigate pregnant women's knowledge of their body mass index (BMI) and their knowledge of gestational weight gain guidelines. METHODS: Participants were recruited when attending their nuchal translucency scan at between 11 and 13 weeks, 6-days gestation in Dunedin or Christchurch, New Zealand. Recruitment staff measured participants' weight and height. By way of a self-administered, paper-based survey, participants were asked to identify their body size (including: underweight (BMI <18.5 kg/m2); normal weight (18.5-24.9); overweight (25-29.9); and obese (≥30)), and recommended gestational weight gain (including the 2009 Institute of Medicine guidelines for healthy weight gain in pregnancy, along with the options: "I should not gain any weight in my pregnancy", plus "It does not matter how much weight I gain"). Participant-measured BMI was compared to responses for perceived BMI and recommended gestational weight gain to assess accuracy. Demographic predictors of accuracy were also investigated. RESULTS: In total, 644 women were included. Sixty-six percent of these correctly identified their BMI category, however only 31% identified their correct gestational weight gain recommendation. Overweight and obese women were much more likely to underestimate their BMI than normal weight women (p<0.001 for both). Overweight and obese women were also more likely to overestimate their weight gain recommendation (OR=4, p<0.001; OR=18, p<0.001, respectively) while normal weight women were more likely to underestimate their weight gain recommendation (p<0.001). Independent of BMI, women of New Zealand European ethnicity were less likely to underestimate their recommended gestational weight gain compared to other women of non-Maori/non-Pacific Island ethnicity (p=0.001), whereas younger women (p=0.012) were more likely to underestimate recommended gestational weight gain. CONCLUSION: The present study indicates that New Zealand women, particularly those who are overweight and obese, lack accurate knowledge of their own body size, and this may lead to an under- or over-estimation of appropriate gestational weight gain, which may in turn lead to increased risk of poor health outcomes in pregnancy. Education strategies related to healthy weight gain in pregnancy are urgently required.

An early pregnancy HbA1c ≥5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes.

OBJECTIVE: Pregnant women with undiagnosed diabetes are a high-risk group that may benefit from early intervention. Extrapolating from nonpregnancy data, HbA1c ≥6.5% (48 mmol/mol) is recommended to define diabetes in pregnancy. Our aims were to determine the optimal HbA1c threshold for detecting diabetes in early pregnancy as defined by an early oral glucose tolerance test (OGTT) at <20 weeks' gestation and to examine pregnancy outcomes relating to this threshold. RESEARCH DESIGN AND METHODS: During 2008-2010 in Christchurch, New Zealand, women were offered an HbA1c measurement with their first antenatal bloods. Pregnancy outcome data were collected. A subset completed an early OGTT, and HbA1c performance was assessed using World Health Organization criteria. RESULTS: HbA1c was measured at a median 47 days' gestation in 16,122 women. Of those invited, 974/4,201 (23%) undertook an early OGTT. In this subset, HbA1c ≥5.9% (41 mmol/mol) captured all 15 cases of diabetes, 7 with HbA1c <6.5% (<48 mmol/mol). This HbA1c threshold was also 98.4% (95% CI 97-99.9%) specific for gestational diabetes mellitus (GDM) before 20 weeks (positive predictive value = 52.9%). In the total cohort, excluding women referred for GDM management, women with HbA1c of 5.9-6.4% (41-46 mmol/mol; n = 200) had poorer pregnancy outcomes than those with HbA1c <5.9% (<41 mmol/mol; n = 8,174): relative risk (95% CI) of major congenital anomaly was 2.67 (1.28-5.53), preeclampsia was 2.42 (1.34-4.38), shoulder dystocia was 2.47 (1.05-5.85), and perinatal death was 3.96 (1.54-10.16). CONCLUSIONS: HbA1c measurements were readily performed in contrast to the low uptake of early OGTTs. HbA1c ≥5.9% (≥41 mmol/mol) identified all women with diabetes and a group at significantly increased risk of adverse pregnancy outcomes.

Weight and height measurement: potential impact in obstetric care.

AIM: To assess the accuracy of reported weight and height in a pregnant population. METHODS: Participants were recruited when attending their nuchal translucency scan if they attended with an 'antenatal screening for Down syndrome and other conditions' laboratory form (used for the maternal serum screening in the first trimester (MSS1) blood test) that had weight and/or height recorded. Participants' weight and height were measured by trained recruitment centre staff and body mass index (BMI) was calculated. Differences in reported (MSS1) and measured weight, height and BMI were analysed using Bland-Altman plots. RESULTS: 248 women participated. Only 23% (n=56) of participants had a weight recorded on the MSS1 laboratory form that was within plus or minus 0.5 kg of measured weight: 62% (n=155) had an under-reported weight, and 15% (n=37) an over-reported weight. 30% (n=74) of participants had a correctly reported height: 26% (n=63) an under-reported height, and 44% (n=107) an over-reported height. 6% (n=14) of participants had a correctly reported BMI: 69% (n=166) had an under-reported BMI, and 25% (n=60) an over-reported BMI. 17% of participants (n=40) were incorrectly classified by BMI category based on MSS1 data. CONCLUSION: Our study suggests that there are considerable inaccuracies in the recording of weight and height during pregnancy in New Zealand. This results in a false reduction in BMI in many women which can affect clinical care.

C-type natriuretic peptide in complicated pregnancy: increased secretion precedes adverse events.

CONTEXT: C-type natriuretic peptide (CNP), a vasoactive product of the endothelium, is markedly increased during placentation in ovine pregnancy and is further stimulated by nutrient restriction. Whether CNP products change in human pregnancy is unknown. OBJECTIVES: The objective of the study was to compare serial changes in maternal plasma CNP peptides during normal pregnancy with changes in pregnancy complicated by adverse events and relate these to fetal growth and placental CNP content. DESIGN: This was a prospective observational study undertaken in a tertiary care center. METHODS: We studied changes in maternal plasma aminoterminal proCNP (NTproCNP) and CNP at monthly intervals, fetal growth, and placental and umbilical plasma CNP peptides in 51 women, 28 of whom experienced an adverse event and 23 were uneventful. Age matched healthy nonpregnant women served as a reference range for NTproCNP. RESULTS: Compared with nonpregnant women, maternal plasma NTproCNP in an uneventful pregnancy was significantly reduced from first sampling (16 wk gestation) until 36 weeks. In contrast, in complicated pregnancy, levels did not decline and were significantly higher (P < .001 by ANOVA) than in normal pregnancy from 20 weeks. Highest values occurred in women later developing hypertension and fetal growth disorders. Placental concentration of NTproCNP was unrelated to maternal NTproCNP but strongly correlated with cord plasma levels. CONCLUSIONS: Maternal NTproCNP is significantly raised in women who later exhibit a range of obstetric adverse events. Lack of association with placental concentrations suggests that these changes represent an adaptive response within the maternal circulation to a threatened nutrient supply to the fetus.

Characterization of the tissue-level Ca2+ signals in spontaneously contracting human myometrium.

In the labouring uterus, millions of myocytes forming the complex geometrical structure of myometrium contract in synchrony to increase intrauterine pressure, dilate the cervix and eventually expel the foetus through the birth canal. The mechanisms underlying the precise coordination of contractions in human myometrium are not completely understood. In the present study, we have characterized the spatio-temporal properties of tissue-level [Ca(2+)](i) transients in thin slices of intact human myometrium. We found that the waveform of [Ca(2+)](i) transients and isotonic contractions recorded from thin slices was similar to the waveform of isometric contractions recorded from the larger strips in traditional organ bath experiments, suggesting that the spatio-temporal information obtained from thin slices is representative of the whole tissue. By comparing the time course of [Ca(2+)](i) transients in individual cells to that recorded from the bundles of myocytes we found that the majority of myocytes produce rapidly propagating long-lasting [Ca(2+)](i) transients accompanied by contractions. We also found a small number of cells showing desynchronized [Ca(2+)](i) oscillations that did not trigger contractions. The [Ca(2+)](i) oscillations in these cells were insensitive to nifedipine, but readily inhibited by the T-type Ca(2+) channel inhibitor NNC55-0396. In conclusion, our data suggest that the spread of [Ca(2+)](i) signals in human myometrium is achieved via propagation of long-lasting action potentials. The propagation was fast when action potentials propagated along bundles of myocytes and slower when propagating between the bundles of uterine myocytes.

Phase-plot analysis of the oxytocin effect on human myometrial contractility.

OBJECTIVE: Analysis of uterine contractility in vitro is usually confined to measuring a few traditional parameters of uterine contractility, such as contraction amplitude, frequency and area under the curve. In this paper, we describe parameters that provide additional information obtained from the traces of force and its first derivative. We propose an improved contractility index which is less dependent on variability between samples. STUDY DESIGN: Standard organ bath recording of myometrial contractions in the presence or absence of oxytocin on samples of human myometrium obtained from 26 patients at Caesarean section. The parameters were obtained from the plots of first derivative vs. contractile force (phase portrait plot). RESULTS AND CONCLUSIONS: Oxytocin (1nM) significantly increased the contraction amplitude (Fmax), area under the curve, maximum rate of contraction (CVmax), decreased the maximum rate of relaxation (RVmax) and had no statistically significant effect on the duration of contraction (measured as full width at half amplitude, W50). In addition to the above effects, 10nM oxytocin increased the contraction duration (P=0.0036, n=24). The fraction of force developed at the time of CVmax showed no change at any concentration of oxytocin, while the fraction of force remaining at RVmax was decreased in a dose dependent manner. The least variable (i.e. showing lowest P values in paired Student's t-Test) parameters were the Fmax and CVmax/RVmax. When non-paired t-Test was applied, P value of the CVmax/RVmax remained low, while the variability of Fmax increased reflecting the sample-to-sample variations. The product of the Fmax and CVmax/RVmax, which we propose as uterine contractility index (CI) showed low P values in both paired and non-paired t-Tests. We conclude that the phase plot analysis provides useful additional information on contraction/relaxation properties of human myometrium and the CI is suitable for characterising the contractility of uterine samples with different connective tissue content.

Control of uterine Ca2+ by membrane voltage: toward understanding the excitation-contraction coupling in human myometrium.

Myometrial contractility is a complex and dynamic physiological process that changes substantially during pregnancy and culminates in childbirth. Uterine contractions are initiated by transient rises in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)), which in turn are triggered and controlled by myometrial action potentials. The sequence of events between the action potential generation and the contraction initiation is referred to as excitation-contraction coupling. Hormones and other physiologically active substances affect myometrial contractility by modulating different steps in the excitation-contraction coupling process. It is therefore imperative that we understand that process to understand the regulation of myometrial contractility. The complex action potentials generated by human myometrium result from the activity of many ion channels, transporters, and pumps. Two types of myometrial action potential waveform have been described in the literature: a plateau type and a spike type. Parameters of the myometrial [Ca(2+)](i) transients and contractions differ depending on the type of action potential that triggers them. Some aspects of the excitation-contraction coupling are unique to human myometrium and cannot be found in animal models; some others are common between many species. This article reviews the current state and discusses future directions of physiological research on human myometrial excitation-contraction coupling.

Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility.

Oxytocin is a small peptide hormone with multiple sites of action in human body. It regulates a large number of reproduction-related processes in all species. Particularly important is its ability to stimulate uterine contractility. This is achieved by multiple mechanisms involving sarcoplasmic reticulum Ca2+ release and sensitization of the contractile apparatus to Ca2+. In this paper, we review the data published by us and other groups on oxytocin-induced modulation of uterine contractility. We conclude that sensitization of contractile apparatus to Ca2+ is the most relevant physiological effect of oxytocin on human myometrium.