Etiology Of Preterm Labor Research Articles

The role of the microbiome in pregnancy.

To provide a comprehensive overview of the available information on the maternal microbio-me and its effect on pregnancy and preterm birth. Systematic review of available literature on the topic was done using the PubMed database. Etiology of preterm labor is multifactorial. Individual setting of humoral and cellular immune response is key; however, lately the focus has shifted to the role of the microbio-me, especially the vaginal one. The role of additional microbio-mes and the relationship between different compartments are the focus of intensive research. Mainly the differences in the maternal and neonatal microbio-me depend on the method of delivery and administration of different antibio-tics during pregnancy and labor. The uterine cavity is no longer thought to be without colonization and the formation of the fetal microbio-me begins early in pregnancy.

IS AMNIOTIC FLUID ANALYSIS DURING THE SECOND TRIMESTER A PREDICTOR FOR THE DETECTION OF PRETERM LABOR?

Objective: Premature activation of the hypothalamic-pituitary-adrenal axis due to stress can initiate preterm labor. Many mechanisms have been proposed to explain etiopathogenesis. The most important one is clinical and subclinical chorioamnionitis. We aimed to assess the possibility of early detection and prevention of preterm labor based on second trimester amniotic fluid analysis. Material and Method: One hundred and twenty-five pregnant women with singleton pregnancies who underwent amniocentesis were included. The first 2 cm3 of the amniotic fluid obtained during the amniocentesis was used for glucose, interleukin-1, interleukin-6, high sensitivity C-reactive protein, electrolytes, progesterone/estrogen analysis, and cell counts. Results: Sixteen women (13.8%) went into labor prior to 37 weeks of gestation. The mean age of the study population was 33.2±6.25 years. Ages were similar between the preterm and term groups (36.06±3.91 vs 32.77±6.43). Furthermore, the analysis of all parameters in the amniotic fluid did not show any statistical significant difference between the groups. Conclusion: The possible effects of subclinical infection and steroid hormonal changes that are implied in the etiology of preterm labor were investigated in our study, and no evidence was found to support that these factors played a role in the etiology of preterm labor. 

The role of 25-hydroxyvitamin D (25(OH)D) in preterm labor

Premature labor is the greatest cause of death for children under 5 years old worldwide. The etiology of preterm labor is often unknown. Some concepts that explain the causes of premature labor are basically always associated with the incidence of infections in the amniotic fluid, utero-placental ischemia, excessive uterine strains, endocrine disorders, and abnormal immune responses from the mother and fetus. Vitamin D plays an important role as an antiinflammatory and antimicrobial agent, so the purpose of this study is to examine the role of 25-hydroxyvitamin D (25(OH)D), which can prevent preterm labor. This is a literature review of related studies. Vitamin D functions in the regulation of calcium and phosphate in the blood. Some studies also explain that vitamin D has a function in regulating the immune system, participating in mitosis and cell differentiation, in the expression of nitric oxide synthesis (NOS), glutathione synthesis and neurotrophic factors. Low vitamin D levels have been shown to be significantly associated with an increased risk of preterm birth in several countries such as India and China. Vitamin D has a significant role in the mechanism of preterm labor.

Assessment of Maternal-Fetal outcomes by Doppler Flow Velocity Waveforms in Preterm Labor Patients Undergoing Magnesium Sulfate Tocolysis

Background: Preterm labor is frequency uterine contractions, pro- gressive effacement and dilation of the cervix prior to term gestation. Prevention and treatment of preterm labor is important because it is one of the most important causes of perinatal morbidity and mortali- ty. The etiology of preterm labor is poorly understood. Aim of the Work: to evaluate the influence of antenatally admin- istrated magnesium sulfate (MgSO4) given to women at risk of preterm birth on the cerebral blood flow and systemic hemodynamic in preterm infants. Patients and Methods: This was a prospective observational in- terventional study conducted from October 2016 to February 2017 on (40) patients undergoing preterm labor at AL Zahraa hospital Al Azhar university and New Cairo Hospital, after informed a written consent was taken from every patient after counseling them the pro- cedure of the study. Results: In our study we found that the best blood level of magne- sium sulfate at which contractions stopped (cut off) is (>4.18) mg/dl which equal (6.82) gm of administrated magnesium sulfate with sen- sitivity (94.74%) and specificity (100%), positive predictive value (PPV) was (100%) and negative predictive value (NPV) was (50%). Conclusion: Maternal magnesium sulphate (Mgso4) decreases the cerebral perfusion pressure and blood flow, and this likely protects the germinal matrix against the development of circulatory stress in the early post natal period. Magnesium sulphate achived the primary outcome (prevention of delivery for 48 hours, with uterine quies- cence) at cut-off value of (≥4.18) mg/dl which equal (6.82) gm with sensitivity (94.74%), specificity (100%), positive predictive value (100%) negative predictive value (50%).

The importance of the smooth muscle cytoskeleton to preterm labour

Multiple mechanisms have been shown to regulate the onset of labour in a co-operative and complex manner. One factor, myometrial stretch and associated increases in wall tension, has been implicated clinically in the initiation of labour and especially the aetiology of preterm labour. Recent work on the mechanisms involved has led to the finding that the intracellular Ca(2+) requirement for activation of the myometrial contractile filaments increases during gestation. The decreased Ca(2+) sensitivity correlates with an increase in the expression of caldesmon, an actin-binding protein and inhibitor of myosin activation, during pregnancy. In late pregnancy, an increase in extracellular signal-regulated kinase-mediated caldesmon phosphorylation occurs, which appears to reverse the inhibitory action of caldesmon during labour. Force generated by the myometrial contractile filaments is communicated across the plasmalemma to the uterine wall through focal adhesions. Phospho-tyrosine screening and mass spectrometry of stretched myometrial samples identified several stretch-activated focal adhesion proteins. This Src-mediated focal adhesion signalling appears to provide a tunable, i.e. regulated, tension sensor and force transmitter in the myometrial cell. In other parallel studies, biophysical measurements of smooth muscle compliance at both the cellular and tissue levels suggest that decreases in cellular compliance due to changing interactions of the actin cytoskeleton with the focal adhesions may also promote increases in uterine wall tension. These results, taken together, suggest that focal adhesion proteins and their interaction with the cytoskeleton may present a new mode of regulation of uterine contractility.

Effect of Maintenance Tocolysis With Nifedipine in Threatened Preterm Labor on Perinatal Outcomes

Preterm birth is the most common cause of neonatal morbidity and mortality worldwide and is associated with long-term burdens. The effectiveness of maintenance tocolysis on pregnancy and perinatal outcomes has not been demonstrated. This multicenter, double-blind, placebo-controlled trial was designed to evaluate the effectiveness of maintenance tocolysis with nifedipine on perinatal outcome. Eligible women had threatened preterm labor at 26 to 32 weeks’ gestation and had not delivered after a 48-hour course of tocolytics and corticosteroids. Study medication was 20 mg nifedipine slow-release tablets every 6 hours, for a total daily dose of 80 mg nifedipine, or placebo. The medication was given 48 to 72 h after the start of initial tocolysis and was phased out from day 10 until day 12 and discontinued on day 13. The primary outcome was a composite of adverse perinatal outcomes due to premature birth. Secondary outcomes were gestational age at delivery, birth weight, days using ventilation support, length of stay in neonatal intensive care unit, and total days in hospital until 3-month corrected age. Exploratory analyses examined prolongation of pregnancy, maternal mortality, maternal blood loss, and infant respiratory distress syndrome. Of 636 eligible women, 406 agreed to participate; 201 received nifedipine, and 205 received placebo. Mean gestational age at randomization was 29.2 weeks for both groups. Adverse perinatal outcomes occurred in 24 cases (11.9%) in the nifedipine group and 28 (13.7%) in the placebo group; perinatal death occurred in 5 (2.5%) and 4 cases (2.0%), respectively. Rates of chronic lung disease, proven neonatal sepsis, intraventricular hemorrhage greater than grade 2, periventricular leukomalacia greater than grade 1, and necrotizing enterocolitis were comparable in the 2 groups. Mean gestational ages at delivery were 34.1 and 34.2 weeks for the nifedipine and placebo groups, respectively. Birth weights did not differ significantly between the 2 groups. Neonatal intensive care unit admission occurred in 100 (40.8%) of 245 neonates in the nifedipine group and in 102 of 257 (39.7%) in the placebo group; neonatal intensive care unit and hospital stays were 10 and 23 days for both groups. The nifedipine and placebo infants required ventilation support for 2 and 3 days, respectively. Women in the 2 groups randomized at different gestational ages had no differences in perinatal mortality, composite adverse perinatal outcome, gestational age at delivery, or birth weight. Delivery before 32 weeks’ gestation occurred in 66 women (32.8%) given nifedipine and 71 women (34.6%) receiving placebo. Infant respiratory distress syndrome treated with surfactant occurred in 12 pregnancies (6.0%) in the nifedipine group and 14 (6.8%) in the placebo group. No mother in either group died. Cesarean deliveries were performed in 26.4% of women given nifedipine and 27.3% of those given placebo. Severe blood loss of more than 1000 mL occurred 11.1% and 7.3% in the nifedipine and placebo groups, respectively. Compared with placebo, nifedipine maintenance tocolysis for 12 days did not significantly reduce adverse perinatal outcomes. The etiology of preterm labor is multifaceted such that future research should investigate therapies targeted to the specific underlying causes of preterm labor.

Blood pH and gases in fetuses in preterm labor with and without systemic inflammatory response syndrome

Objective: Fetal hypoxemia has been proposed to be one of the mechanisms of preterm labor (PTL) and delivery. This may have clinical implications since it may alter: (i) the method/frequency of fetal surveillance and (ii) the indications and duration of tocolysis to an already compromised fetus. The aim of this study was to examine whether there is a difference in the fetal blood gas analysis [pH, PaO2 and base excess (BE)] and in the prevalence of fetal acidemia and hypoxia between: (i) patients in PTL who delivered within 72 hours vs. those who delivered more than 72 hours after cordocentesis and (ii) patients with fetal inflammatory response syndrome (FIRS) vs. those without this condition. Study design: Patients admitted with PTL underwent amniocentesis and cordocentesis. Ninety women with singleton pregnancies and PTL were classified according to (i) those who delivered within 72 hours (n = 30) and after 72 hours of the cordocentesis (n = 60) and (ii) with and without FIRS. FIRS was defined as a fetal plasma concentration of IL-6 > 11 pg/mL. Fetal blood gases were determined. Acidemia and hypoxemia were defined as fetal pH and PaO2 below the 5th percentile for gestational age, respectively. For comparisons between the two study groups, ΔpH and ΔPaO2 were calculated by adjusting for gestational age (Δ = observed value – mean for gestational age). Non-parametric statistics were employed. Results: No differences in the median Δ pH (−0.026 vs. −0.016), ΔPaO2 (0.25 mmHg vs. 5.9 mmHg) or BE (−2.4 vs. −2.6 mEq/L) were found between patients with PTL who delivered within 72 hours and those who delivered 72 hours after the cordocentesis (p > 0.05 for all comparisons). Fetal plasma IL-6 concentration was determined in 63% (57/90) of fetuses and the prevalence of FIRS was 28% (16/57). There was no difference in fetal pH, PaO2 and BE between fetuses with and without FIRS (p > 0.05 for all comparisons). Moreover, there was no difference in the rate of fetal acidemia between fetuses with and without FIRS (6.3 vs. 9.8%; p > 0.05) and fetal hypoxia between fetuses with or without FIRS (12.5 vs. 19.5%; p > 0.05). Conclusions: Our data do not support a role for acute fetal hypoxemia and metabolic acidemia in the etiology of PTL and delivery.

Association of glutathione S-transferase M1 and T1 gene polymorphisms and oxidative stress markers in preterm labor

Objective Oxidative stress and related gene polymorphism may be associated with the etiology of preterm labor (PTL). The present study was designed to investigate association of GSTM1 and GSTT1 gene polymorphisms with PTL and their relationship with oxidative stress markers. Design and methods Sixty cases of PTL and sixty three subjects of full term labor (FTL) were included in the study. Multiplex PCR was performed for GSTM1 and GSTT1 genes polymorphism and oxidative stress markers were analyzed. Result MDA and 8-OHdG levels were increased, while GSH was decreased in PTL than FTL subjects. Frequency of GSTM1− /GSTT1−(null) was significantly higher in PTL in comparison to FTL ( p = 0.028, OR = 3.4). Subjects with GSTM1− /GSTT1+, GSTM1+/GSTT1− , GSTM1− /GSTT1− have significant differences of oxidative stress markers as compared to GSTM1+/GSTT1+ genotype. Conclusion GSTM1− /GSTT1− (null) genotype may be one of the associated genetic factor for the increased risk of PTL.

Stretch Activates Human Myometrium via ERK, Caldesmon and Focal Adhesion Signaling

An incomplete understanding of the molecular mechanisms responsible for myometrial activation from the quiescent pregnant state to the active contractile state during labor has hindered the development of effective therapies for preterm labor. Myometrial stretch has been implicated clinically in the initiation of labor and the etiology of preterm labor, but the molecular mechanisms involved in the human have not been determined. We investigated the mechanisms by which gestation-dependent stretch contributes to myometrial activation, by using human uterine samples from gynecologic hysterectomies and Cesarean sections. Here we demonstrate that the Ca requirement for activation of the contractile filaments in human myometrium increases with caldesmon protein content during gestation and that an increase in caldesmon phosphorylation can reverse this inhibitory effect during labor. By using phosphotyrosine screening and mass spectrometry of stretched human myometrial samples, we identify 3 stretch-activated focal adhesion proteins, FAK, p130Cas, and alpha actinin. FAK-Y397, which signals integrin engagement, is constitutively phosphorylated in term human myometrium whereas FAK-Y925, which signals downstream ERK activation, is phosphorylated during stretch. We have recently identified smooth muscle Archvillin (SmAV) as an ERK regulator. A newly produced SmAV-specific antibody demonstrates gestation-specific increases in SmAV protein levels and stretch-specific increases in SmAV association with focal adhesion proteins. Thus, whereas increases in caldesmon levels suppress human myometrium contractility during pregnancy, stretch-dependent focal adhesion signaling, facilitated by the ERK activator SmAV, can contribute to myometrial activation. These results suggest that focal adhesion proteins may present new targets for drug discovery programs aimed at regulation of uterine contractility.

Prevention of Inflammatory Activation of Human Gestational Membranes in an Ex Vivo Model Using a Pharmacological NF-κB Inhibitor

Intrauterine inflammation plays a major role in the etiology of preterm labor and birth. We established an ex vivo model employing perfused full-thickness term gestational membranes to study membrane transport, function, and inflammatory responses. Exposure of the maternal (decidual) face of the membranes to LPS (5 microg/ml) resulted in increased accumulation of proinflammatory cytokines in the maternal compartment within 4 h, followed by a response in the fetal (amniotic) compartment. Using cytokine arrays, exposure to LPS was found to result in increased secretion of a large number of cytokines and chemokines in both compartments, most notably IL-5, IL-6, IL-7, MDC (macrophage-derived chemokine), MIG (monokine induced by IFN-gamma), TARC (thymus and activation-regulated chemokine), TGF-beta, and TNF-alpha. PGE(2) accumulation also increased in response to LPS, particularly in the fetal compartment. Cotreatment with sulfasalazine, which inhibited nuclear translocation of NF-kappaB p65, had a rapid and marked inhibitory effect on the rate of cytokine accumulation in the maternal compartment, with lesser but significant effects observed in the fetal compartment. While membrane integrity was not discernibly impaired with LPS or sulfasalazine exposure, rates of chorionic apoptosis after 20 h were doubled in sulfasalazine-treated tissues. We conclude that the system described provides a means of accurately modeling human gestational membrane functions and inflammatory activation ex vivo. Decidual LPS exposure was shown to elicit a robust inflammatory response in both the maternal and fetal compartments. Sulfasalazine was an effective antiinflammatory agent in this model, but also exerted proapoptotic effects that raise concerns regarding its placental effects when administered in pregnancy.

Aetiology of preterm labour: bacterial vaginosis

Bacterial vaginosis (BV) is a common condition characterised by a polymicrobial disorder, with an overgrowth of several anaerobic or facultative bacteria and with a reduction or absence of lactobacillus colonisation. The prevalence of BV ranges from 4 to 64%, depending on the racial, geographic and clinical characteristics of the study population. In asymptomatic women, the prevalence varies from 12 to 25%, and similar percentages are observed in pregnant women. Although BV is associated with several adverse outcomes, such as upper genital tract infections, pelvic inflammatory disease, endometritis, preterm birth and low birthweight, many basic questions regarding the pathogenesis of BV remain unanswered. Mucosal immune system activation may represent a critical determinant of adverse consequences associated with BV. An unequal risk for BV acquisition and\or recurrence could derive from different mucosal immune host abilities and\or capability of invading microbes to produce factors that inactivate the local immune response. BV is associated with a two-fold increased risk of preterm birth, with the greatest risk when BV is present before 16 weeks of gestation (odds ratio = 7.55). This may indicate a critical period during early gestation when BV-related organisms can gain access to the upper genital tract and set the stage for spontaneous preterm labour later in gestation. The results of treatment trials for pregnant women with BV have been heterogeneous, with anywhere from an 80% reduction to a two-fold increase in preterm birth among women who received treatment. For this reason, in current clinical practice significant controversy surrounds determining not only who and when to screen but also who and how to treat. Recent evidence shows that individual genetic backgrounds can affect chemokine production. This is an interesting area for future research and could lead to trials of treatment only for women genetically predisposed to preterm birth.

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Prävention und Therapie der vorzeitigen Wehentätigkeit* - Prevention and Treatment of Preterm Labor -

Objective: The incidence of preterm birth has remained unchanged for years at about 8-10%. Prematurity remains the leading cause of neonatal mortality, accounting for 70-85% of all neonatal deaths, so that the prevention and treatment of preterm labor is a central issue in pregnancy care. Methods: We review possible risk factors for preterm labor and strategies for prevention and treatment. Results: Although infections play an important role in the etiology of preterm labor, antibiotics should not be used prophylactically without evidence of infection in patients with intact membranes. In contrast, a beneficial effect for antibiotics has been proved for preterm premature rupture of the membranes. Only 10-20% of women with preterm labor have an indication for tocolytic treatment. The use of tocolytics before 24 and after 36 weeks' gestation should be limited to special situations. Tocolytic treatment with intravenous β 2 -sympatheticomimetic agents can significantly reduce the rate of delivery within 48 hours, a period sufficient to reduce the risk for the respiratory distress syndrome with corticosteroids. In contrast, the efficacy of longterm parenteral tocolysis or oral tocolysis is unproved. In certain situations tocolysis can be achieved with intravenous magnesium, nifedipine, or inhibitors of prostaglandin synthesis. The psychosocial situation should also be taken into account because there is evidence that psychologic aspects play a role in the etiology of preterm labor.

Macrophage trafficking in the uterus and cervix precedes parturition in the mouse.

Immune activation is implicated in the etiology of preterm labor, but little is known about macrophage number or distribution in the uterus or cervix at term. This study tested the hypothesis that macrophages migrate into the reproductive tract before the onset of parturition. Paraffin-embedded sections from the mid-uterine horn and cervix of C3/HeN mice on Days 15 and 18 of pregnancy, the day of birth (Day 19), and 1 day postpartum were stained with a pan-macrophage marker to analyze cell numbers and distribution. During pregnancy, uterine macrophages were dispersed in endometrium, usually associated with vasculature and subluminal epithelium. In myometrium, macrophages were clustered in stromal connective tissue; near term and postpartum, cells appeared to surround the muscle bundles. Total macrophage numbers were increased on Day 15 relative to those in nonpregnant controls, declined before birth, and increased postpartum. In the cervix, macrophages congregated in subepithelium, often perivascular or near ganglia. Macrophage numbers in the cervix peaked on Day 18, then declined to nonpregnant levels by the day after birth. Thus, macrophage numbers in the uterus were inversely related to those in the cervix. These findings raise the possibility that macrophages and their products may be involved in uterine contractility and cervical remodeling during the processes of parturition.

The Mouse as an Investigational Model for Preterm Labor

Preterm labor continues to be a leading cause of perinatal morbidity and mortality. In many cases the etiology of preterm labor is unknown. However, much interest has been generated surrounding the infectious causes of preterm labor. Because data suggest that preterm labor is preceded by a cascade of complex events, in vivo observations in humans and in vitro experiments using human tissue may not be sufficient to answer questions regarding its etiology. The murine model holds significant promise in delineating the chronology and specifics regarding the events precipitating preterm labor.

Preterm birth prevention

The prevention of preterm birth may be the most important problem facing maternity care providers. Preterm birth occurs in 10% of all births in the United States and is associated with 83% of perinatal deaths not caused by congenital anomalies. This article reviews the anatomy and physiology of the uterus, the physiology of uterine contractions, the initiation of labor, the etiology of preterm labor, risk factors and risk scoring for preterm labor, and the diagnosis and management of preterm labor. The components of a preterm birth prevention program are described, and recommendations for clinical practice are made.

2 Chorioamnionitis and pre-term delivery

Chorioamnionitis is strictly defined as inflammation of the chorioamniotic membranes. The term has occasionally been used to indicate the clinical syndrome of infection within the amniotic cavity but this is more appropriately termed amniotic infection syndrome. Although chorioamnionitis has generally been associated with clinical amniotic infection and pre-term labour some authors have considered it to be a non-specific inflammation of minimal perinatat significance (Driscoll et al, 1973). This apparent contradiction is due, at least in part, to differences to histological techniques and pathological criteria. Chorioamnionitis begins with an initially patchy polymorphonuclear leukocyte infiltration into the chorion which becomes more diffuse to involve the fetal surface of the amnion and the placenta. Preparation of fetal membrane rolls for histological examination allows a large area to be examined and diffuse chorioamnionitis to be distinguished from small areas of inflammation, for example at the site of membrane rupture. Pre-term labour, defined as labour before 37 weeks of amenorrhoea, remains a significant problem in obstetric practice. It occurs in up to 10% of all births but is associated with 85% of perinatal deaths in otherwise normal babies (Rush et al, 1976) and accounts for an unknown proportion of physical and mental handicap. Multiple pregnancy, polyhydramnios or Miillerian anomalies account for only a minority of cases of pre-term labour; in most cases the cause is unknown. The most reliable predictor that a woman will deliver pre-term is that she had done so in a previous pregnancy. Pre-term labour is weakly associated with advanced maternal age, cigarette smoking, high parity, and poor socioeconomic status (Newcombe and Chalmers, 1981). Only in the past decade has the role of infection or abnormal colonization of the genital tract been recognized as a major factor in the aetiology of pre-term labour.

Infection and preterm labour

Preterm labour occurs in up to 10% of all births but is associated with 85% of perinatal deaths in otherwise normal babies and an unknown proportion of physical and mental handicap. The cause of preterm labour is usually unknown. Cases associated with multiple pregnancy, polyhydramnios or abnormalities of the uterus or cervix are in the minority. Associations have been found between preterm labour and maternal age, weight and height, cigarette smoking, parity, and other socio-economic factors.’ Recently the role of infection has been recognised as a major factor in the aetiology of preterm labour. The evidence that preterm labour is associated with genital tract infection falls into three categories; the increased incidence of puerpural sepsis following preterm delivery; the increased incidence of infection in premature neonates; and the epidemiological association between preterm labour and genital tract colonisation by various organisms. The incidence of maternal puerpural sepsis is three-fold greater following preterm labour than delivery at term. The incidence of infection in premature neonates is 5% compared to O.l-0.5% in term infants.3 This is partly a reflection of their immaturity, their increased risk of instrumentation and exposure to hospital pathogens in the neonatal intensive care unit. It is likely, however, that many of these infections are acquired in utero or during vaginal delivery. Common causes of neonatal sepsis are the group B streptococci and Escherichia coli both of which are commonly found in the vagina.

The significance of infection in the aetiology of preterm labour. A prospective controlled study

SummaryBacteriological examinations were made of 100 women and their babies. Three groups were studied; those in preterm labour, and 2 control groups, threatened preterm labour and uncomplicated mature labour. Chorio-amnionitis was present in 25 per cent of the preterm labour patients, which was the only group to present with clinical signs. Unlike other reports, this study did not demonstrate a high colonisation rate of Chlamydia, Ureaplasma urealyticum and Mycoplasma. This may be a reflection of the study population and the low incidence of preterm labour in this district. Sexual activity during pregnancy showed no significant correlation with preterm deliveries, premature rupture of membranes, the bacteriological findings or the presence of histological or clinical chorio-amnionitis.

The aetiology of preterm labour

Factors associated with spontaneous preterm birth were analysed in 254 primigravidae who gave birth to singleton infants between 28 and 36 completed weeks gestation in Aberdeen City District between 1978 and 1982. In 144 women labour followed premature rupture of the membranes and in 110 the membranes were intact and labour began with contractions. Among those with intact membranes, unmarried women and teenagers were over represented to a significant extent compared with all primigravidae. Among those with premature rupture of the membranes, the distribution of age and marital state was similar to that in all primigravidae, but the birthweight centile distribution showed a significant shift towards light-for-dates babies. It is argued that there may be two distinct categories of pregnancies that end in spontaneous preterm labour.