Comparative study of the enzyme activities of Borrelia burgdorferi and other non-intestinal and intestinal spirochaetes

Recurrent pregnancy loss is a healthcare concern. Safe and effective treatments are necessary. Since women experiencing recurrent pregnancy loss are a heterogeneous population, specific markers are necessary to identify those who will respond to various treatments. The presence of antiphospholipid antibodies identifies women with recurrent pregnancy loss who are most likely to respond to heparin and aspirin treatment. An elevated concentration of NK cells in maternal blood and a loss of karyotypically normal embryos after detection of cardiac activity on ultrasonographic examination identify women who are most likely to respond to IVIg treatment. An obstetric history of recurrent primary abortion with an absence of maternal antipaternal lymphocytotoxic antibodies and anti-phospholipid antibodies predicts women who are most likely to respond to allogeneic leukocyte immunization. However, the treatment effect is low, with a livebirth rate of 60% which represents an enhancement over no treatment in the range of 8-10%. The difference in livebirth rates between women receiving IVIg therapy as compared to placebo was 28%. Women experiencing recurrent spontaneous abortion who have high, as opposed to low levels of leukocyte antibody do not respond to leukocyte immunization therapy. They do, however, respond to treatment with IVIg--the overall success rate of IVIg being 70%. It is important to be able to identify women likely to respond to various forms of immunotherapy. Chromosomal abnormalities are evident in 60% of recurrent aborters. Women experiencing recurrent aneuploidy in their abortus would not be expected to respond to immunotherapy. At the present time, the only way to identify such women is to have the results of chromosome analysis of previous pregnancy losses available. Having access to this information will require a change in current obstetric practice regarding obtaining karyotyping of all pregnancy losses. The cost-effectiveness of chromosome studies from abortuses is apparent when costs of evaluation and treatment are considered.     

Previous cesarean birth. A risk factor for placenta previa?

OBJECTIVE: To study the risk of placenta previa following a previous cesarean birth. STUDY DESIGN: We conducted a population-based, case-control study using 1990 North Carolina state birth certificate data. The study population included 342 women with a pregnancy complicated by placenta previa and 1,082 randomly selected controls. Analysis was restricted to women who reported one or more previous live births and delivered a singleton, live neonate. Adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using logistic regression, controlling for maternal age, race, prior spontaneous or induced abortions and cigarette use. RESULTS: When the data were adjusted for maternal age, race, prior spontaneous or induced abortions, and cigarette use, women who had a previous cesarean birth and had a parity of 3 were 1.7 times more likely (OR 1.7, 95% CI 0.7, 4.2) and women of parity > or = 4 were 5.5 times more likely (OR 5.5, 95% CI 1.0, 30.1) to have placenta previa than women of parity 1 who had a previous cesarean birth. CONCLUSION: Women with a history of a previous cesarean birth and parity > or = 3 were at increased risk of having a pregnancy complicated by placenta previa.     

A cytogenetic study of 514 Chinese couples with recurrent spontaneous abortion

OBJECTIVE: To study the role of chromosomal aberration in the causation of recurrent spontaneous abortion (RSA) in Chinese population. METHODS: A total of 514 Chinese couples with 2 or more spontaneous abortions at less than 24 weeks of gestation were included. For each proband, a minimum of 13 metaphases were analyzed by G-banding. Additional cells (usually 50-100 cells) were screened when mosaicism was suspected. Chi 2 test was used to compare the number and frequency of couples with and without balanced translocation with respect to whether liveborn was present or absent. Chi 2 test for trend was used to show whether a correlation existed between the occurrence of balanced translocation and the number of spontaneous abortions at ascertainment. RESULTS: The overall incidence of chromosome anomaly was 51 out of 514 (9.92%). Chi 2 test for trend analysis showed that the chance of one member of a couple being a balanced carrier increased with the number of spontaneous abortions. The chance of finding translocation in couples with liveborn was higher than that in couples without liveborn, but the difference was not statistically significant. We also found that pericentric inversion 9 did not play an important role in the causation of recurrent abortion. CONCLUSIONS: Cytogenetic analysis is indicated in couples with 2 or more spontaneous abortions and the chance of finding chromosomal aberration increases with the number of abortions at the time of ascertainment.     

Altered interface adhesion molecules in oral lichen planus

Recurrent spontaneous abortion is a frustrating problem for clinicians and their patients. Fortunately, a reasonable amount of research is being conducted to try and identify the causes of this disorder and develop appropriate and effective diagnostic tests and therapies. This review focuses on some of the factors that have been associated with recurrent abortion, such as cell-mediated immune responses to trophoblast antigens, the effect of oxidative stress, and the immunomodulatory properties of placental protein. The risk of recurrence is particularly high when the length of the embryo in early pregnancy is less than the 50th centile, even though cardiac activity may be present. Also, the risk is directly related to the number of previous abortions. Efficacy has been shown for treatment of unexplained recurrent abortion with allogeneic leukocyte immunization and possibly with intravenous immunoglobulin. Patients with oligomenorrhoea may benefit from treatment with human chorionic gonadotropin.     

Weakness of biochemical markers of nutritional and inflammatory status as prognostic indices for growth retardation and morbidity of young children in central Africa

BACKGROUND: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss. METHODS: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy. RESULTS: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02). CONCLUSIONS: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.     

Inhibitory serum factor of lymphoproliferative response to allogeneic cells in pregnancy

INTRODUCTION: An inhibitory serum factor of mixed lymphocyte culture (MLC) has been associated with successful pregnancy after lymphocyte transfusion in women with unexplained recurrent spontaneous abortions (RSA). OBJECTIVE: Investigate whether the inhibitory serum factor of MLC is essential for a successful pregnancy. METHOD: Sera from 33 healthy pregnant women and from 40 women with RSA were assessed by a one-way MLC in which the woman's lymphocytes were stimulated with her partner's lymphocytes or with third party lymphocytes. RESULTS: An inhibitory serum effect (inhibition > 50% as compared to normal serum) was detected in 45% of the pregnant women who had at least 1 previous parity, in 8% of the primigravidea, in 29% of those with one abortion and in 58% of those with more than one abortion. CONCLUSION: MLC inhibitory serum factor does not seem to be an essential factor for pregnancy development. Therefore, it should not be considered as a parameter for the assessment of RSA patients.     

Authors'' experience with transvaginal administration of progestagens]

Prognostic value of some clinical factors on the course of subsequent pregnancy in 117 women with unexplained recurrent spontaneous abortion undergoing immunization with paternal lymphocytes were evaluated in the study. The results allow to conclude that high efficiency of alloimmunization in preventing consecutive abortions (87.2% in our own study) does not seem to depend significantly on: the woman's and her partner's age, number, type (primary vs. secondary), and time of previous miscarriages, coexistence of subfertility, time from immunization to the fertilization and the number of lymphocytes used for the procedure (as far as it concerns the number of lymphocytes isolated from 100 ml of blood). In our results, alloimmunization is most effective in preventing a missed abortion (in comparison with "live" spontaneous abortion).     

Automobile accidents in patients with sleep apnea syndrome. An epidemiological and mechanistic study

AIM: To compare the pregnancy outcome, in particular gestational age and birth weight in women with systemic lupus erythematosus (SLE) diagnosed before and after pregnancy, and to review data on presence or absence of the antiphospholipid (aPL) antibody and flares of disease activity. METHOD: Case histories were reviewed of women with a diagnosis of SLE and an obstetric event attending Monash Medical Centre (MMC) over an eight year period (1988-96). Fifty-four pregnancies in 28 women were studied, with 44 occurring after the diagnosis of SLE (Group 1) and ten prior to the diagnosis of SLE (Group 2). RESULTS: In Group 1 there were 25 live births (63%) with 16 full term and nine premature deliveries, 12 spontaneous abortions, three foetal deaths in utero and four elective terminations. In Group 2 there were seven live births (70%), two spontaneous abortions and one foetal death in utero. The mean gestational age of live births was 35.8 weeks and 39.2 weeks respectively (p < 0.001). The mean birth weight of live births was 2448 g and 3030 g respectively (p < 0.023). a PL antibodies were positive in eight of 26 women tested with three live births and were negative in 18 of 26 women with 12 live births. Flares of disease activity occurred in 17 of 28 pregnancies. CONCLUSION: Pregnancy in women with a predisposition to SLE have a high risk of an adverse outcome. Clinical disease confers an additional risk. The mean gestational age and birth weight were significantly less in women with established disease. Mild flares in disease activity resulted in a favourable outcome while renal flares had a worse outcome.     

Update on immunotherapy for recurrent pregnancy loss

Results of recent, randomized, placebo-controlled clinical trials have raised questions about the efficacy of immunotherapy for recurrent spontaneous abortion (RSA). Most of the clinical trials have shown a 70% successful pregnancy rate with immunotherapy. The controversy comes from variations in success rates in the control populations, which have ranged from 29% to 76%. Explanations for these variations includes small sample sizes and heterogeneity by the populations studied as well as cointervention by the placebo. A meta-analysis has been proposed to investigate these explanations. Because the trials have largely used husband's leukocytes for immunization, alternative forms of immunotherapy have been sought. Two treatments that have been proposed but have not completed testing a randomized, placebo-controlled trials are intravenous immunoglobulin (IVIG) and immunization with seminal plasma. A safe and efficacious method is needed to treat recurrent spontaneous abortion; it is hoped that results of proposed studies will answer this controversy.     

Prevalence of Down's syndrome in Asturias, 1987-1993. Members of the Work Group of the RCDA

OBJECTIVE: To determine the frequency of Down Syndrome (DS) in Asturias and the prenatal diagnosis impact on the birth prevalence of this chromosomal anomaly. METHODS: The analysed data came from the Registry of Congenital Defects of Asturias (1990-1993) and from a retrospective study conducted by the same working group (1987-1989). The total prevalence rates and the prevalence at birth were calculated. RESULTS: Out of 55,601 births, DS was recorded in 83 cases: 69 livebirths, two fetal deaths and 12 induced abortions following prenatal diagnosis, giving a total prevalence rate of 14.9 per 10,000 and a birth prevalence of 12.8. The proportion of induced abortions was 15 per cent in this period; the proportion of cases in the high risk maternal age group (35 years and over) was around 50% of the total. The proportion of induced abortions was 15 per cent in this period. CONCLUSIONS: The frequency of DS in Asturias is comparable to the other populations. Prenatal diagnosis had little impact on the birth prevalence figures. These results may help us draw up prevention and prenatal diagnosis policies for these defects in Asturias when giving the frequency of this health problem.     

Chlamydial serologic studies and recurrent spontaneous abortion

OBJECTIVE: Our purpose was to investigate the putative association between immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortions. STUDY DESIGN: Sera from 106 idiopathic recurrent aborters and 81 of their partners were tested for immunoglobulin G antichlamydial antibodies by whole inclusion immunofluorescence and compared with 3890 sera from a general antenatal population. Positive sera were further investigated by microimmunofluorescence to determine species (Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci) specificity. RESULTS: Twenty-six (24.5%) of women with recurrent spontaneous abortions had immunoglobulin G antichlamydial antibodies compared with 28 (34.6%) of their partners (chi 2 2.25, p < 0.05) and 788 (20.3%) of the general antenatal population (chi 2 1.16, p < 0.05), and the incidence of antibody positivity showed no trend with increasing number of previous abortions. Fourteen women with recurrent spontaneous abortions had antibodies to Chlamydia trachomatis, 12 to Chlamydia pneumoniae. The prevalence of antibodies to C. trachomatis did not differ significantly between women with recurrent spontaneous abortions and their partners, but the male partners had a significantly (p = 0.005) higher prevalence of Chlamydia pneumoniae antibodies. Chlamydial antibody seropositivity did not correlate with subfertility or subsequent pregnancy outcome. CONCLUSION: There is no association between immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortion.     

The effect of Rh-D immunoprophylaxis with hyperimmune anti-D-immunoglobulin on the occurrence of RhD immunization in pregnancy

During prenatal immunohaematological examination in the period from January 1, 1991 to December 31, 1995, in the Croatian Institute of Transfusion Medicine we tested sera of 5107 RhD negative women. All of them had pregnancies in their medical history. The frequency of Rh immunization was 4.6% in 1991; 4.1% in 1992; 2.5% in 1993; 2.5% in 1994 and 2.4% in 1995. Rh immunization during the first pregnancy was observed in 0.46% of women, in 1.8% during the second, in 9.4% during the third, in 22.4% during the fourth pregnancy, and 33.8% in women with more than five pregnancies. In women that have no abortions in their medical history, anti-D alloantibodies were found with the frequency of 0.46% at the end of the first pregnancy, 1.2% at the end of the second pregnancy, 5.9% at the end of the third pregnancy, 14.3% at the end of the fourth pregnancy, and 15.3% in women with more than five pregnancies. The frequency of anti-D alloantibodies in women who in their medical history have only abortions is 3.4% after the first abortion, 10.5% after the second, 17.8% after the third and 20.8% after the fourth or more abortions. The frequency of antibodies of anti-D specificities in women who had abortions and births is 17.1% at the end of the third pregnancy, 26.2% at the end of the fourth pregnancy, and 42.7% after more than five pregnancies. The frequency of anti-D alloantibodies in women who were protected from Rh immunization by hyperimmune anti-D globulin is 1%. The obtained results demonstrate that prevention of Rh immunization by hyperimmune anti-D globulin does not comprise all the Rh negative women, and is especially inadequate after abortions and multiple pregnancies.     

Air pollution and daily mortality in Seoul and Ulsan, Korea

Prenatal diagnosis of chromosomal disorders has been performed for more than 20 years, mainly for advanced maternal age. Chromosomal abnormality rates derived from second trimester amniocentesis have mainly come from a collection of small-scale studies from North America and Western Europe. Accurate risk estimates for chromosomal abnormalities are important tools for the physician or obstetrician who would need to make referrals to a prenatal genetic center. This paper presents amniocentesis rates of clinically significant cytogenetic abnormalities for various indications, including advanced maternal age, previous chromosomal abnormality, parental structural rearrangement and a family history of aneuploidy as defined in the text. These data come from a Canadian prenatal diagnosis laboratory with more than 20 years experience in second trimester cytogenetic analysis. They show that the overall frequency of chromosomal abnormalities for advanced maternal age (> or = 35 years) is 1.79%. In this group, 21% of all abnormalities are structural rearrangements (including markers) and less than half of all abnormalities are trisomy 21. The advanced maternal age specific risk of aneuploidies at second trimester is 1.24%. Recurrence risk for aneuploidy after a previous one is 1.29%. However, it is much higher (4.84%) for women of > or = 35 years. When a parent's brother, sister, nephew or niece is affected, the risk of occurrence of aneuploidies (0.24%) is not elevated. When there is a balanced translocation in one of the parents, the overall risk is 10.2% for unbalanced translocations and 37.3% for balanced translocations.     

Metabolic risk factors in patients with first-time and recurrent stone formations as determined by comprehensive metabolic evaluation

OBJECTIVES: To determine whether patients with recurrent calcium stone formation have more significant metabolic abnormalities compared with patients with first-time stone formation as determined by a comprehensive metabolic evaluation. METHODS: We investigated metabolic abnormalities in 37 patients (14 men, 23 women) with first-time and 136 patients (83 men, 53 women) with recurrent calcium stones, stratified according to sex. Calcium oxalate supersaturation indexes of Tiselius (1991) and Ogawa (1996) were also compared between the groups. In addition to the specific metabolic abnormalities, we analyzed the total number of such defects for each group. RESULTS: In men, the average number of metabolic abnormalities in each patient was greater in patients with recurrent stones (2.20+/-0.86) than in those with first-time stones (1.46+/-1.27). Such a difference could only be demonstrated for women if low urine volume was excluded as a specific abnormality. Although the frequency of each abnormality was higher in patients with recurrent stones, a statistically significant difference was only noted in the frequency of hypocitraturia between women with first-time and recurrent stone formation (11.1% versus 37.8%, P < 0.05). There were no significant differences in the calcium oxalate supersaturation indexes between first-time and recurrent stone formation in either men or women. CONCLUSIONS: Women with recurrent stones have a higher prevalence of hypocitraturia than women with first-time stones. Potassium citrate therapy for prevention of urolithiasis may be especially useful for this patient population.     

Increased risk of placenta previa among women of Asian origin

OBJECTIVE: To investigate the frequency of placenta previa among Asian women. METHODS: We conducted a population-based case-control study using Washington state birth certificate data from 1984-1987. Our study population included 810 women with pregnancies complicated by placenta previa and 2917 randomly selected controls. Unconditional logistic regression was used to estimate odds ratios (OR) and their 95% confidence intervals (CI), and interaction terms were used to examine effect modification. Potential confounding by maternal age, gravidity and parity, maternal smoking during pregnancy, and a history of abortion or cesarean delivery was adjusted for in the analysis. RESULTS: The frequency of placenta previa during the study period was 3.3 per 1000 live births. Women of Asian origin were 86% more likely (OR 1.86, 95% CI 1.38-2.51) to have a delivery complicated by placenta previa than were white women. This association was stronger among women without a previous live birth (OR 2.51, 95% CI 1.57-4.01) than those who previously had experienced a live birth (OR 1.50, 95% CI 1.01-2.25). CONCLUSION: Asian women residing in the United States are at increased risk of placenta previa. If confirmed by others, our results suggest that obstetricians should consider meticulous ultrasound evaluations during pregnancy to rule out the presence of placenta previa in Asian-American women.     

HLA-DR typing of women with recurrent late spontaneous abortion and unsuccessful cervical cerclage

The release of certain cytokines, e.g. tumour necrosis factor (TNF)-alpha, in the amniotic fluid has been suggested to be a cause of preterm birth. The predisposition to excessive liberation of cytokines from peripheral leukocytes has been shown to depend partly on the individual's HLA-DR genotype. The HLA-DR1 and -DR3 alleles have previously been reported as being associated with a TNF-alpha high responder status and have also been associated with unexplained recurrent spontaneous abortions. In the present study, HLA-DR typing was performed in 10 women who had experienced recurrent very early preterm births resulting in perinatal death, or late spontaneous abortions under a clinical picture resembling that traditionally attributed to cervical incompetence. All patients had had at least one mid-trimester miscarriage in spite of the insertion of a cervical cerclage. Nine out of 10 (90%) patients had the HLA-DR phenotypes DR1 and/or DR3 compared with 37% in the background population (P < 0.005). The results suggest that HLA-DR-associated immunological factors might play a part in recurrent late spontaneous abortions and extremely preterm births under a cervical incompetence-like picture, at least in the subset of cases not treatable by cervical cerclage.     

A case-control study of reproductive factors and risk of lymphomas and myelomas

The relationship between reproductive factors and risk of lymphoid neoplasms was investigated in a hospital-based case-control study conducted in northern Italy on women with histologically confirmed incident Hodgkin's disease (HD) (n = 68), non-Hodgkin's lymphomas (NHL) (n = 180) and multiple myelomas (MM) (n = 71), and 448 controls admitted to hospitals, for acute, non-neoplastic, non-immunological and non-gynecological conditions. The odds ratios (OR) of HD were 0.6 for > or = 3 pregnancies compared to nulligravidae, and 0.5 for > or = 1 total (spontaneous and induced) abortions compared to women reporting no abortions. Compared to nulliparae, the OR of HD was 0.9 in parae and 0.3 in those with first birth when aged < 20 years. The OR of NHL and MM in relation to number of pregnancies, abortions and births, age at first birth and time since last birth were close to unity. Results were similar for the relation between reproductive factors and HD in women younger than 50 years. The OR of NHL was above unity (OR 2.2, 95% CI 1.0 to 4.9) for women aged < 50 years reporting one or more pregnancies as compared to nulliparae, and for women reporting the last birth since less than 10 years (OR 2.9, 95% CI 1.1 to 7.4). Early events in pregnancy, including changes in immunological status, rather than exposure to female sex hormones are likely mechanisms for the protection of pregnancies and abortions on the risk of HD.     

Abortion surveillance--United States, 1995

CONDITION: Since 1990 (i.e., the year in which the number of abortions was highest), the annual number of abortions in the United States has decreased by 15%. REPORTING PERIOD COVERED: This report summarizes and reviews information reported to CDC regarding legal induced abortions obtained in the United States during 1995. DESCRIPTION OF SYSTEM: For each year since 1969, CDC has compiled abortion data received from 52 reporting areas: 50 states, the District of Columbia, and New York City. RESULTS: In 1995, a total of 1,210,883 legal abortions were reported to CDC, representing a 4.5% decrease from the number reported for 1994. The abortion ratio was 311 legal induced abortions per 1,000 live births, and the abortion rate was 20 per 1,000 women aged 15-44 years, the lowest ratio and rate recorded since 1975. Women who were undergoing an abortion were more likely to be young, white, and unmarried; most were obtaining an abortion for the first time. Approximately half of all abortions (54%) were performed at < or =8 weeks of gestation, and approximately 88% were performed before 13 weeks. Approximately 16% of abortions were performed at the earliest weeks of gestation (< or =6 weeks), approximately 17% at 7 weeks of gestation, and approximately 21% at 8 weeks of gestation. Few abortions were provided after 15 weeks of gestation -- approximately 4% of abortions were obtained at 16-20 weeks, and 1.4% were obtained at > or =21 weeks. Younger women (i.e., women aged < or =24 years) were more likely to obtain abortions later in pregnancy than were older women. INTERPRETATION: Since 1990, the number of abortions has declined each year. Since 1987, the abortion-to-live-birth ratio has declined; in 1995, it was the lowest recorded since 1975. This decrease in the abortion ratio reflects a trend that a lower proportion of pregnant women obtain induced abortion. ACTIONS TAKEN: The number and characteristics of women who obtain abortions in the United States should continue to be monitored so that trends in induced abortion can be assessed, efforts to prevent unintended pregnancy can be evaluated, and the preventable causes of morbidity and mortality associated with abortions can be identified and reduced.     

Human leukocyte antigen class II genotype in patients with recurrent fetal miscarriage who are positive for anticardiolipin antibody

OBJECTIVE: To elucidate the relationship between human leukocyte antigen (HLA) class II genotypes and patients with recurrent fetal miscarriage who are positive for anticardiolipin antibody. DESIGN: Prospective clinical study. SETTING: Institutional practice at the outpatient clinic for infertility, Niigata University Medical Hospital. PATIENT(S): Patients with recurrent fetal miscarriage who were positive for anticardiolipin antibody and normal fertile women. INTERVENTION(S): Genomic DNA was extracted from peripheral mononuclear cells. MAIN OUTCOME MEASURE(S): Human leukocyte antigen class II genotype was determined using a polymerase chain reaction restriction fragment length polymorphism method. RESULT(S): The frequencies of DRB1*0403 and DRB1*0410 were significantly higher in the patient group than in the control group. The frequency of DRB1*04 also was significantly higher in the patient group. As for HLA-DQ genotype, the frequency of HLA-DQB1*0501 was significantly lower in the patient group. CONCLUSION: Human leukocyte antigen systems appear to be involved in the genesis of antiphospholipid syndrome.     

Sex ratios: are there natural variations within the human population?

OBJECTIVE: To investigate on a population basis the suggestion that certain factors naturally alter the odds of having a boy or a girl, and that some women are predisposed towards having children of one particular gender. DESIGN: Routine data analysis. POPULATION: Routinely collected data on singleton infants born in Scotland from 1975 to 1988, linked so that births (live and still) to the same mother could be identified. The analyses relate to 549,048 first to fifth order births occurring to 330,088 women whose records were complete from the first delivery onwards. MAIN OUTCOME MEASURES: Gender of infant. RESULTS: Of 549,048 births, 51.4% were male. Apart from random variation, the sex ratio of 1.06 remained constant at all birth orders (P = 0.18). The probability of a male infant appeared unrelated to the genders of the preceding siblings (P > 0.20 in second to fifth deliveries), and there was no evidence of variation with maternal age (P = 0.31), maternal height (P = 0.69), paternal social class (P = 0.12), maternal social class (P = 0.57), year of delivery (P = 0.84) or season of birth (P = 0.41). Whilst mothers whose children were all the same gender were more likely to continue childbearing than those with children of different genders, there was no evidence that those with daughters were more likely to continue than those with sons. CONCLUSIONS: The suggestion that some women have a natural predisposition towards having children of a particular gender is not supported by these data. On a population basis there is no evidence to suggest that gender determination is anything other than a chance process.