Showing papers on "Pregnancy published in 2004"

Regulatory T cells mediate maternal tolerance to the fetus.

Abstract: Pregnancy constitutes a major challenge to the maternal immune system, as it has to tolerate the persistence of paternal alloantigen Although localized mechanisms contribute to fetal evasion from immune attack, maternal alloreactive lymphocytes persist We demonstrate here an alloantigen-independent, systemic expansion of the maternal CD25+ T cell pool during pregnancy and show that this population contains dominant regulatory T cell activity In addition to their function in suppressing autoimmune responses, maternal regulatory T cells suppressed an aggressive allogeneic response directed against the fetus Their absence led to a failure of gestation due to immunological rejection of the fetus

The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes.

Abstract: The prevalence of smoking during pregnancy varies markedly across countries. In many industrialized countries, prevalence rates appear to have peaked and begun to decline, whereas in other countries smoking is becoming increasingly common among young women. Randomized controlled trials have shown that smoking interventions during pregnancy have had limited success. Smoking during pregnancy is in many countries recognized as the most important preventable risk factor for an unsuccessful pregnancy outcome. Smoking is causally associated with fetal growth restriction, and increasing evidence also suggests that smoking may cause stillbirth, preterm birth, placental abruption, and possibly also sudden infant death syndrome. Smoking during pregnancy also is generally associated with increased risks of spontaneous abortions, ectopic pregnancies, and placenta previa and may increase risks of behavioral disorders in childhood. Smoking during pregnancy will continue to be an important risk factor for maternal and fetal outcomes during pregnancy.

Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies

Abstract: Objective To compare the perinatal outcome of singleton and twin pregnancies between natural and assisted conceptions. Design Systematic review of controlled studies published 1985-2002. Studies reviewed 25 studies were included of which 17 had matched and 8 had non-matched controls. Main outcome measures Very preterm birth, preterm birth, very low birth weight, low birth weight, small for gestational age, caesarean section, admission to neonatal intensive care unit, and perinatal mortality. Results For singletons, studies with matched controls indicated a relative risk of 3.27 (95% confidence interval 2.03 to 5.28) for very preterm ( < 32 weeks) and 2.04 (1.80 to 2.32) for preterm ( < 37 weeks) birth in pregnancies after assisted conception. Relative risks were 3.00 (2.07 to 4.36) for very low birth weight ( < 1500 g), 1.70 (1.50 to 1.92) for low birth weight ( < 2500 g), 1.40 (1.15 to 1.71) for small for gestational age, 1.54 (1.44 to 1.66) for caesarean section, 1.27 (1.16 to 1.40) for admission to a neonatal intensive care unit, and 1.68 (1.11 to 2.55) for perinatal mortality. Results of the non-matched studies were similar. In matched studies of twin gestations, relative risks were 0.95 (0.78 to 1.15) for very preterm birth, 1.07 (1.02 to 1.13) for preterm birth, 0.89 (0.74 to 1.07) for very low birth weight, 1.03 (0.99 to 1.08) for low birth weight, 1.27 (0.97 to 1.65) for small for gestational age, 1.21 (1.11 to 1.32) for caesarean section, 1.05 (1.01 to 1.09) for admission to a neonatal intensive care unit, and 0.58 (0.44 to 0.77) for perinatal mortality. The non-matched studies mostly showed similar trends. Conclusions Singleton pregnancies from assisted reproduction have a significantly worse perinatal outcome than non-assisted singleton pregnancies, but this is less so for twin pregnancies. In twin pregnancies, perinatal mortality is about 40% lower after assisted compared with natural conception.

Low birthweight: country regional and global estimates.

Abstract: Low birthweight has been defined by the World Health Organization (WHO) as weight at birth of less than 2500 grams (5.5 pounds). This practical cut-off for international comparison is based on epidemiological observations that infants weighing less than 2500 g are approximately 20 times more likely to die than heavier babies. More common in developing than developed countries a birthweight below 2500 g contributes to a range of poor health outcomes. The goal of reducing low birthweight incidence by at least one third between 2000 and 2010 is one of the major goals in ‘A World Fit for Children’ the Declaration and Plan of Action adopted at the United Nations General Assembly Special Session on Children in 2002. The reduction of low birthweight also forms an important contribution to the Millennium Development Goal (MDG) for reducing child mortality. Activities towards the achievement of the MDGs will need to ensure a healthy start in life for children by making certain that women commence pregnancy healthy and well nourished and go through pregnancy and childbirth safely. Low birthweight is therefore an important indicator for monitoring progress towards these internationally agreed-upon goals. (excerpt)

Predicting Preschooler Obesity at Birth: The Role of Maternal Obesity in Early Pregnancy

Abstract: Objective. Knowing risk factors at birth for the development of childhood obesity could help to identify children who are in need of early obesity prevention efforts. The objective of this study was to determine whether children whose mothers were obese in early pregnancy were more likely to be obese at 2 to 4 years of age. Methods. A retrospective cohort study was conducted of 8494 low-income children who were enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in Ohio and were followed from the first trimester of gestation until 24 to 59 months of age. Measured height and weight data from WIC were linked to birth certificate records for children who were born in the years 1992–1996. Obesity among 2- to 4-year-olds was defined as a body mass index (BMI) ≥95th percentile for age and gender. Mothers were classified as obese (BMI ≥30 kg/m 2 ) or nonobese (BMI 2 ) on the basis of BMI measured in the first trimester of the child’s gestation. Results. The prevalence of childhood obesity was 9.5%, 12.5%, and 14.8% at 2, 3, and 4 years of age, respectively, and 30.3% of the children had obese mothers. By 4 years of age, 24.1% of children were obese if their mothers had been obese in the first trimester of pregnancy compared with 9.0% of children whose mothers had been of normal weight (BMI ≥18.5 and 2 ). After controlling for the birth weight, birth year, and gender of the children plus the mothers’ age, race/ethnicity, education level, marital status, parity, weight gain, and smoking during pregnancy, the relative risk of childhood obesity associated with maternal obesity in the first trimester of pregnancy was 2.0 (95% confidence interval [CI]: 1.7–2.3) at 2 years of age, 2.3 (95% CI: 2.0–2.6) at 3 years of age, and 2.3 (95% CI: 2.0–2.6) at 4 years of age. Conclusion. Among low-income children, maternal obesity in early pregnancy more than doubles the risk of obesity at 2 to 4 years of age. In developing strategies to prevent obesity in preschoolers, special attention should be given to newborns with obese mothers.

Epidemiology of preterm birth

Abstract: Preterm birth is a major challenge in perinatal health care. Most perinatal deaths occur in preterm infants, and preterm birth is an important risk factor for neurological impairment and disability. Preterm birth not only affects infants and their families—providing care for preterm infants, who may spend several months in hospital, has increasing cost implications for health services. Preterm birth is the delivery of a baby before 37 completed weeks' gestation. Most mortality and morbidity affects “very preterm” infants (those born before 32 weeks' gestation), and especially “extremely preterm” infants (those born before 28 weeks of gestation). Definitions of preterm live births by completed weeks of gestation Over the past 20-30 years advances in perinatal care have improved outcomes for infants born after short gestations. The number of weeks of completed gestation that defines whether a birth is preterm rather than a fetal loss has become smaller. In 1992 the boundary that required registration as a preterm live birth in the United Kingdom was lowered from 28 completed weeks' gestation to 24 weeks' gestation. This boundary varies internationally, however, from about 20 to 24 weeks. Some classification of fetal loss, still birth, and early neonatal death for these very short gestations may be unreliable. Even in developed countries, there is often uncertainty and incomplete recording of estimates of gestation. In most of the United Kingdom data on birth weight data but not on gestational age are collected routinely. Although some concordance exists between the categories of birth weight and gestational age, they are not interchangeable. The categories for birth weight are: Only around two thirds of …

Prenatal glucocorticoids and long-term programming.

Abstract: Epidemiological evidence suggests that low birth weight is associated with an increased risk of cardiovascular, metabolic and neuroendocrine disorders in adult life. Glucocorticoid administration during pregnancy reduces offspring birth weight and alters the maturation of the lung and other organs. We hypothesised that prenatal exposure to excess glucocorticoids or stress might represent a mechanism linking foetal growth with adult pathophysiology. In rats, birth weight is reduced following prenatal exposure to the synthetic steroid dexamethasone, which readily crosses the placenta, or to carbenoxolone, which inhibits 11b-hydroxysteroid dehydrogenase type 2 (11b-HSD2), the physiological fetoplacental ‘barrier’ to maternal glucocorticoids. As adults, the offspring exhibit permanent hypertension, hyperglycaemic, increased hypothalamic-pituitary-adrenal (HPA) axis activity and behaviour reminiscent of anxiety. Physiological variations in placental 11b-HSD2 activity correlate directly with foetal weight. In humans, 11b-HSD2 gene mutations cause low birth weight. Moreover, lowbirth-weight babies have higher plasma cortisol levels throughout adult life, indicating HPA axis programming. The molecular mechanisms may reflect permanent changes in the expression of specific transcription factors, key among which is the glucocorticoid receptor (GR) itself. The differential programming of the GR in different tissues reflects effects upon one or more of the multiple tissue-specific alternate first exons/promoters of the GR gene. Overall, the data suggest that both pharmacological and physiological exposure prenatally to excess glucocorticoids programmes cardiovascular, metabolic and neuroendocrine disorders in adult life. European Journal of Endocrinology 151 U49–U62

Prenatal and Postnatal Environmental Tobacco Smoke Exposure and Children’s Health

Abstract: Children's exposure to tobacco constituents during fetal development and via environmental tobacco smoke (ETS) exposure is perhaps the most ubiquitous and hazardous of children's environmental exposures. A large literature links both prenatal maternal smoking and children's ETS exposure to decreased lung growth and increased rates of respiratory tract infections, otitis media, and childhood asthma, with the severity of these problems increasing with increased exposure. Sudden infant death syndrome, behavioral problems, neurocognitive decrements, and increased rates of adolescent smoking also are associated with such exposures. Studies of each of these problems suggest independent effects of both pre- and postnatal exposure for each, with the respiratory risk associated with parental smoking seeming to be greatest during fetal development and the first several years of life.

Role of thyroid hormone during early brain development.

Abstract: The present comments are restricted to the role of maternal thyroid hormone on early brain development, and are based mostly on information presently available for the human fetal brain. It emphasizes that maternal hypothyroxinemia - defined as thyroxine (T4) concentrations that are low for the stage of pregnancy - is potentially damaging for neurodevelopment of the fetus throughout pregnancy, but especially so before midgestation, as the mother is then the only source of T4 for the developing brain. Despite a highly efficient uterine-placental 'barrier' to their transfer, very small amounts of T4 and triiodothyronine (T3) of maternal origin are present in the fetal compartment by 4 weeks after conception, with T4 increasing steadily thereafter. A major proportion of T4 in fetal fluids is not protein-bound: the 'free' T4 (FT4) available to fetal tissues is determined by the maternal serum T4, and reaches concentrations known to be of biological significance in adults. Despite very low T3 and 'free' T3 (FT3) in fetal fluids, the T3 generated locally from T4 in the cerebral cortex reaches adult concentrations by midgestation, and is partly bound to its nuclear receptor. Experimental results in the rat strongly support the conclusion that thyroid hormone is already required for normal corticogenesis very early in pregnancy. The first trimester surge of maternal FT4 is proposed as a biologically relevant event controlled by the conceptus to ensure its developing cerebral cortex is provided with the necessary amounts of substrate for the local generation of adequate amounts of T3 for binding to its nuclear receptor. Women unable to increase their production of T4 early in pregnancy would constitute a population at risk for neurological disabilities in their children. As mild-moderate iodine deficiency is still the most widespread cause of maternal hypothyroxinemia in Western societies, the birth of many children with learning disabilities may already be preventable by advising women to take iodine supplements as soon as pregnancy starts, or earlier if possible.

Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset.

Abstract: Summary CD4+ CD25+ T regulatory cells (TReg), suppress antigen-specific immune responses and are important for allograft tolerance. During pregnancy the mother tolerates an allograft expressing paternal antigens (the fetus) requiring substantial changes in immune regulation over a programmed period of time. We analysed whether immune-suppressive TReg cells were altered during pregnancy and therefore might play a part in this tolerant state. The presence of TReg cells was assessed in the blood of 25 non-pregnant, 63 pregnant and seven postnatal healthy women by flow cytometry. We observed an increase in circulating TReg cells during early pregnancy, peaking during the second trimester and then a decline postpartum. Isolated CD25+ CD4+ cells expressed FoxP3 messenger RNA, a marker of TReg cells, and suppressed proliferative responses of autologous CD4+ CD25- T cells to allogeneic dendritic cells. These data support the concept that normal pregnancy is associated with an elevation in the number of TReg cells which may be important in maintaining materno-fetal tolerance.

Use of chemotherapy during human pregnancy

Abstract: When cancer is diagnosed in a pregnant woman, life-saving chemotherapy for the mother poses life-threatening concerns for the developing fetus. Depending on the type of cancer and the stage at diagnosis, chemotherapy cannot necessarily be delayed until after delivery. Women diagnosed with acute lymphoblastic leukaemia who decline both termination and chemotherapy often die with the previable fetus in utero. Safe use of chemotherapy, especially during the second and third trimester, have been reported, and pregnant women with cancer can accept therapy without definite neonatal harm. Here, we review the use of chemotherapy in pregnancy by trimester of exposure and summarise neonatal outcomes, including malformations, perinatal complications, and oldest age of neonatal follow-up. We will also discuss the modes of action of the drugs used and look at the multiagent regimens recommended for use during pregnancy.

Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands

Abstract: Objective To investigate maternal, perinatal, and neonatal outcomes of pregnancies in women with type 1 diabetes in the Netherlands. Design Nationwide prospective cohort study. Setting All 118 hospitals in the Netherlands. Participants 323 women with type 1 diabetes who became pregnant between 1 April 1999 and 1 April 2000. Main outcome measures Maternal, perinatal, and neonatal outcomes of pregnancy. Results 84% (n = 271) of the pregnancies were planned. Glycaemic control early in pregnancy was good in most women (HbA 1c  7.0% in 75% (n = 212) of the population), and folic acid supplementation was adequate in 70% (n = 226). 314 pregnancies that went beyond 24 weeks9 gestation resulted in 324 infants. The rates of pre-eclampsia (40; 12.7%), preterm delivery (101; 32.2%), caesarean section (139; 44.3%), maternal mortality (2; 0.6%), congenital malformations (29; 8.8%), perinatal mortality (9; 2.8%), and macrosomia (146; 45.1%) were considerably higher than in the general population. Neonatal morbidity (one or more complications) was extremely high (260; 80.2%). The incidence of major congenital malformations was significantly lower in planned pregnancies than in unplanned pregnancies (4.2% (n = 11) v 12.2% (n = 6); relative risk 0.34, 95% confidence interval 0.13 to 0.88). Conclusion Despite a high frequency of planned pregnancies, resulting in overall good glycaemic control (early) in pregnancy and a high rate of adequate use of folic acid, maternal and perinatal complications were still increased in women with type 1 diabetes. Neonatal morbidity, especially hypoglycaemia, was also extremely high. Near optimal maternal glycaemic control (HbA 1c  7.0%) apparently is not good enough.

The Association Between Adverse Childhood Experiences and Adolescent Pregnancy, Long-Term Psychosocial Consequences, and Fetal Death

Abstract: Objectives. Few reports address the im- pact of cumulative exposure to childhood abuse and fam- ily dysfunction on teen pregnancy and consequences commonly attributed to teen pregnancy. Therefore, we examined whether adolescent pregnancy increased as types of adverse childhood experiences (ACE score) in- creased and whether ACEs or adolescent pregnancy was the principal source of elevated risk for long-term psy- chosocial consequences and fetal death. Design, Setting, and Participants. A retrospective co- hort study of 9159 women aged >18 years (mean 56 years) who attended a primary care clinic in San Diego, Cali- fornia in 1995-1997. Main Outcome Measure. Adolescent pregnancy, psy- chosocial consequences, and fetal death, compared by ACE score (emotional, physical, or sexual abuse; expo- sure to domestic violence, substance abusing, mentally ill, or criminal household member; or separated/divorced parent). Results. Sixty-six percent (n 6015) of women re- ported >1 ACE. Teen pregnancy occurred in 16%, 21%, 26%, 29%, 32%, 40%, 43%, and 53% of those with 0, 1, 2, 3, 4, 5, 6, and 7 to 8 ACEs. As the ACE score rose from zero to 1t o 2, 3t o 4, and>5, odds ratios for each adult consequence increased (family problems: 1.0, 1.5, 2.2, 3.3; financial problems: 1.0, 1.6, 2.3, 2.4; job problems: 1.0, 1.4, 2.3, 2.9; high stress: 1.0, 1.4, 1.9, 2.2; and uncontrollable anger: 1.0, 1.6, 2.8, 4.5, respectively). Adolescent preg- nancy was not associated with any of these adult out- comes in the absence of childhood adversity (ACEs: 0). The ACE score was associated with increased fetal death after first pregnancy (odds ratios for 0, 1-2, 3- 4, and 5- 8 ACEs: 1.0, 1.2, 1.4, and 1.8, respectively); teen pregnancy was not related to fetal death. Conclusions. The relationship between ACEs and ad- olescent pregnancy is strong and graded. Moreover, the negative psychosocial sequelae and fetal deaths com- monly attributed to adolescent pregnancy seem to result from underlying ACEs rather than adolescent pregnancy per se. Pediatrics 2004;113:320 -327; adolescent pregnancy, child abuse, domestic violence, alcoholism, children of impaired parents, drug abuse.

Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings.

Abstract: The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congenital hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions.

Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse.

Abstract: The influence of pregnancy in multiple sclerosis has been a matter of controversy for a long time. The Pregnancy in Multiple Sclerosis (PRIMS) study was the first large prospective study which aimed to assess the possible influence of pregnancy and delivery on the clinical course of multiple sclerosis. We report here the 2-year post-partum follow-up and an analysis of clinical factors which might predict the likelihood of a relapse in the 3 months after delivery. The relapse rate in each trimester up to the end of the second year post-partum was compared with that in the pre-pregnancy year. Clinical predictors of the presence or absence of a post-partum relapse were analysed by logistic regression analysis. Using the best multivariate model, women were classified as having or not having a post-partum relapse predicted, and this was compared with the observed outcome. The results showed that, compared with the pre-pregnancy year, there was a reduction in the relapse rate during pregnancy, most marked in the third trimester, and a marked increase in the first 3 months after delivery. Thereafter, from the second trimester onwards and for the following 21 months, the annualized relapse rate fell slightly but did not differ significantly from the relapse rate recorded in the pre-pregnancy year. Despite the increased risk for the 3 months post-partum, 72% of the women did not experience any relapse during this period. Confirmed disability continued to progress steadily during the study period. Three indices, an increased relapse rate in the pre-pregnancy year, an increased relapse rate during pregnancy and a higher DSS (Kurtzke's Disability Status Scale) score at pregnancy onset, significantly correlated with the occurrence of a post-partum relapse. Neither epidural analgesia nor breast-feeding was predictive. When comparing the predicted and observed status, however, only 72% of the women were correctly classified by the multivariate model. In conclusion, the results for the second year post-partum confirm that the relapse rate remains similar to that of the pre-pregnancy year, after an increase in the first trimester following delivery. Women with greater disease activity in the year before pregnancy and during pregnancy have a higher risk of relapse in the post- partum 3 months. This is, however, not sufficient to identify in advance women with multiple sclerosis who are more likely to relapse, especially for planning therapeutic trials aiming to prevent post-partum relapses.

Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals?

Abstract: The incidence of the metabolic syndrome, a cluster of abnormalities focusing on insulin resistance and associated with high risk for cardiovascular disease and diabetes, is reaching epidemic proportions. Prevalent in both developed and developing countries, the metabolic syndrome has largely been attributed to altered dietary and lifestyle factors that favour the development of central obesity. However, population-based studies have suggested that predisposition to the metabolic syndrome may be acquired very early in development through inappropriate fetal or neonatal nutrition. Further evidence for developmental programming of the metabolic syndrome has now been suggested by animal studies in which the fetal environment has been manipulated through altered maternal dietary intake or modification of uterine artery blood flow. This review examines these studies and assesses whether the metabolic syndrome can be reliably induced by the interventions made. The validity of the different species, diets, feeding regimes and end-point measures used is also discussed.

Drug transfer and metabolism by the human placenta

Abstract: The major function of the placenta is to transfer nutrients and oxygen from the mother to the foetus and to assist in the removal of waste products from the foetus to the mother. In addition, it plays an important role in the synthesis of hormones, peptides and steroids that are vital for a successful pregnancy. The placenta provides a link between the circulations of two distinct individuals but also acts as a barrier to protect the foetus from xenobiotics in the maternal blood. However, the impression that the placenta forms an impenetrable obstacle against most drugs is now widely regarded as false. It has been shown that that nearly all drugs that are administered during pregnancy will enter, to some degree, the circulation of the foetus via passive diffusion. In addition, some drugs are pumped across the placenta by various active transporters located on both the fetal and maternal side of the trophoblast layer. It is only in recent years that the impact of active transporters such as P-glycoprotein on the disposition of drugs has been demonstrated. Facilitated diffusion appears to be a minor transfer mechanism for some drugs, and pinocytosis and phagocytosis are considered too slow to have any significant effect on fetal drug concentrations. The extent to which drugs cross the placenta is also modulated by the actions of placental phase I and II drug-metabolising enzymes, which are present at levels that fluctuate throughout gestation. Cytochrome P450 (CYP) enzymes in particular have been well characterised in the placenta at the level of mRNA, protein, and enzyme activity. CYP1A1, 2E1, 3A4, 3A5, 3A7 and 4B1 have been detected in the term placenta. While much less is known about phase II enzymes in the placenta, some enzymes, in particular uridine diphosphate glucuronosyltransferases, have been detected and shown to have specific activity towards marker substrates, suggesting a significant role of this enzyme in placental drug detoxification. The increasing experimental data on placental drug transfer has enabled clinicians to make better informed decisions about which drugs significantly cross the placenta and develop dosage regimens that minimise fetal exposure to potentially toxic concentrations. Indeed, the foetus has now become the object of intended drug treatment. Extensive research on the placental transfer of drugs such as digoxin and zidovudine has assisted with the safe treatment of the foetus with these drugs in utero. Improved knowledge regarding transplacental drug transfer and metabolism will result in further expansion of pharmacological treatment of fetal conditions.

Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case–control study

Abstract: BACKGROUND: Obesity has become a major health problem worldwide and is also associated with adverse pregnancy outcome. The aim of this study was to assess the impact of obesity on the risk of miscarriage in the general public. METHODS: This was a nested case-control study. The study population was identified from a maternity database. Obese [body mass index (BMI) >30 kg/m 2 ] women were compared with an age-matched control group with normal BMI (19-24.9 kg/m 2 ). Only primiparous women were included in the study to avoid including the subject more than once, and to be able to correctly identify recurrent miscarriages. The prevalence of a previous history of early (6-12 weeks gestation), late (12-24 weeks gestation) and recurrent early miscarriages (REM) (more than three successive miscarriages <12 weeks) was compared between the two groups. RESULTS: A total of 1644 obese and 3288 age-matched normal weight controls with a mean age of 26.6 years [95% confidence interval (CI) 26.5-26.7] were included in the study. The risks of early miscarriage and REM were significantly higher among the obese patients (odds ratios 1.2 and 3.5, 95% CI 1.01-1.46 and 1.03-12.01, respectively; P = 0.04, for both]. CONCLUSIONS: Obesity is associated with increased risk of first trimester and recurrent miscarriage.