Abdominal pregnancy in a baboon: a first case report

The abdominal pregnancy is a rare, but life threatening complication of ectopic embryo implantation. Only three cases of abdominal pregnancy have been previously described in primates: in a squirrel monkey, owl monkey and in a rhesus macaque. A 14-year-old wild-caught olive baboon (Papio cynocephalus anubis) was diagnosed at the ultrasound examination with advanced gestational age extrauterine pregnancy. At the initial laparotomy and necropsy the diagnosis of abdominal pregnancy was made on Studdiford's criteria. This case indicates the possibility of developing a model for further study of different types of ectopic pregnancy and indicates a cesarean section as a risk factor for abdominal pregnancy.     

Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study

ObjectiveTo examine the association between hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) and the development of circulatory diseases in later life.DesignCohort study of women who had pre-eclampsia during their first singleton pregnancy. Two comparison groups were matched for age and year of delivery, one with gestational hypertension and one with no history of raised blood pressure.SettingMaternity services in the Grampian region of Scotland.ParticipantsWomen selected from the Aberdeen maternity and neonatal databank who were resident in Aberdeen and who delivered a first, live singleton from 1951 to 1970.ResultsThere were significant positive associations between pre-eclampsia/eclampsia or gestational hypertension and later hypertension in all measures. The adjusted relative risks varied from 1.13-3.72 for gestational hypertension and 1.40-3.98 for pre-eclampsia or eclampsia. The adjusted incident rate ratio for death from stroke for the pre-eclampsia/eclampsia group was 3.59 (95% confidence interval 1.04 to 12.4).ConclusionsHypertensive diseases of pregnancy seem to be associated in later life with diseases related to hypertension. If greater awareness of this association leads to earlier diagnosis and improved management, there may be scope for reducing a proportion of the morbidity and mortality from such diseases.

What is already known on this topic

Much is known about the effect of cardiovascular risks factors that are shared by men and women, but less on those specific to womenRetrospective studies, based on patient recall, suggest that hypertension in pregnancy may be associated with increased risk of cardiovascular diseases in later life

What this study adds

Prospective recording of blood pressure and proteinuria shows that women who experienced raised blood pressure in pregnancy have a long term risk of hypertensionWomen who experience raise blood pressure in pregnancy have an increased risk of stroke and, to a lesser extent, an increased risk of ischaemic heart diseaseLong term cardiovascular risks are greater for women who had pre-eclampsia than those who experienced gestational hypertension (hypertension without proteinuria)     

Relationships of risk factors for pre-eclampsia with patterns of occurrence of isolated gestational proteinuria during normal term pregnancy

Background

Isolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept.

Methods

Data from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy.

Results

Higher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (≤20 weeks gestation), and onset at 21–28 weeks, 29–32 weeks, 33–36 weeks and ≥37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy.

Conclusions

Established pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of pre-eclampsia.     

Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study.

OBJECTIVE: To monitor pregnancies in women with pre-existent insulin dependent diabetes for pregnancy loss, congenital malformations, and fetal growth in a geographically defined area of north west England. DESIGN: Population cohort study. SETTING: 10 maternity units in Cheshire, Lancashire, and Merseyside which had no regional guidelines for the management of pregnancy in diabetic women. SUBJECTS: 462 pregnancies in 355 women with insulin dependent diabetes from the 10 centres over five years (1990-4 inclusive). MAIN OUTCOME MEASURES: Numbers and rates of miscarriages, stillbirths, and neonatal and postneonatal deaths; prevalence of congenital malformations; birth weight in relation to gestational age. RESULTS: Among 462 pregnancies, 351 (76%) resulted in a liveborn infant, 78 (17%) aborted spontaneously, nine (2%) resulted in stillbirth, and 24 (5%) were terminated. Of the terminations, nine were for congenital malformation. The stillbirth rate was 25.0/1000 total births (95% confidence interval 8.9 to 41.1) compared with a population rate of 5.0/1000, and infant mortality was 19.9/1000 live births (5.3 to 34.6) compared with 6.8/1000. The prevalence of congenital malformations was 94.0/1000 live births (63.5 to 124.5) compared with 9.7/1000 in the general population. When corrected for gestational age, mean birth weight in the sample was 1.3 standard deviations greater than that of infants of non-diabetic mothers. Infants with congenital malformations weighed less than those without. CONCLUSION: In an unselected population the infants of women with pre-existent insulin dependent diabetes mellitus have a 10-fold greater risk of a congenital malformation and a fivefold greater risk of being stillborn than infants in the general population. Further improvements in the management of pregnancy in diabetic women are needed if target of the St Vincent declaration of 1989 is to be met.     

A case of Cushing's syndrome in pregnancy

Cushing's syndrome (also known as hypercortisolemia) is rare in pregnant women due to the menstrual disturbances and infertility in women with hypercortisolism. A diagnosis of pathological hypercortisolism in pregnant women is often difficult as some symptoms of the disease may be associated with a complicated pregnancy. Hypercortisolemia leads to serious complications for mother and foetus, and is associated with premature labour and high foetal mortality. Hormonal and radiological diagnostics in pregnancy are limited. The results of hormonal measurements and dynamic tests are difficult to interpret due to the physiological changes in the hypothalamo-pituitaryadrenal axis connected with pregnancy. The optimal time and method of treatment should be chosen cautiously case by case because of the possibility of maternal and foetal complications. In this paper, we present a case of Cushing's syndrome secondary to adrenal adenoma in which the diagnosis was made in the 22(nd) week of pregnancy. Due to the advanced gestational status and mild symptoms of hypercortisolism, only symptomatic treatment was introduced. The patient was under continuous obstetric and endocrinological care. At 35 weeks of gestation, the pregnancy was terminated by emergency caesarean section because of premature detachment of the placenta. A male infant weighing 2,450 g was delivered; neither adrenal insufficiency in the child nor hypercortisolemia complications in the mother were observed.     

Serum leptin in nonpregnant and pregnant women and in old and new world nonhuman primates

Leptin is a hormone that is produced during mammalian pregnancy in the placental trophoblast and other tissues, including! fetal and maternal adipocytes. Synthesis of the polypeptide and the presence of its specific receptors throughout the human maternal fetoplacental unit suggest direct effects on conceptus growth and development. However, both the physiologic roles of leptin and the mechanisms regulating leptin synthesis in human pregnancy differ from those in laboratory and domestic species, necessitating the development of non-human primate research models. Therefore, we compared serum leptin concentrations in nonpregnant and pregnant women with those in both old world nonhuman primates (i.e., baboon, rhesus monkey, cynomolgus monkey) and new world nonhuman primates (i.e., squirrel monkey, titi monkey). As expected, maternal leptin levels were elevated in human and baboon pregnancies (P < 0.05 and P < 0.001, respectively). Levels in both species of old world monkeys were also greatly enhanced (P < 0.001). Although maternal serum concentrations were slightly elevated compared to nonpregnant levels in both species of new world monkeys, overall concentrations were dramatically lower than for either old world primates or humans. Results provide comparisons of serum leptin concentrations in pregnant and nonpregnant humans and baboons with those in both old and new world monkeys and further characterize these nonhuman primates as models for the investigation of leptin dynamics in pregnancy.     

Fetal ultrasonography: biometric data from four African primate species

BACKGROUND: Nonhuman primates are raised in large numbers in research centers and zoos. Reproductive monitoring is required to improve breeding performances. Ultrasonography is a safe method to determine gestational age and to estimate the date of parturition. However only few data are available in nonhuman primates. METHODS: Fetal biometric data were obtained throughout pregnancy on four African primate species, namely chimpanzee, gorilla, mandrill and patas monkey. Measurements included biparietal diameter, transverse abdominal diameter, femur and humerus length, external interorbital diameter, and fetal heart rate. Curves established from these data were compared with previously published data in chimpanzees and gorillas and with those for humans and other closely related primate species. RESULTS: The curves for the different hominids were very similar, while those for mandrills more closely resembled baboons and data for patas monkeys were comparable to those for macaques. CONCLUSIONS: These data, by providing a tool to evaluate precise gestational age, will be useful for centers raising these four primate species.     

Fetomaternal adrenomedullin levels in diabetic pregnancy.

We investigated whether maternal and fetoplacental adrenomedullin, a newly discovered hypotensive peptide involved in the insulin regulatory system, is modified in diabetic pregnancy. We studied its correlation with pregnancy complications associated with this disease. Thirty-six pregnant women with diabetes (13 with type I and 23 with gestational diabetes mellitus) and in 40 uncomplicated pregnancies were included. 10 out of 36 diabetic pregnancies were complicated by gestational hypertension. In each woman, adrenomedullin concentration in maternal and fetal plasma and in amniotic fluid was assessed by specific radioimmunoassay. We found that overall mean amniotic fluid adrenomedullin concentration was higher (p < 0.05) in diabetic (14.7 +/- 1.6 fmol/ml) than in uncomplicated pregnancies (10.8 +/- 0.9 fmol/ml), whereas no differences were present in maternal and fetal plasma adrenomedullin levels between diabetic and uncomplicated pregnant women. High levels of amniotic fluid adrenomedullin were found in both type I and gestational diabetes mellitus pregnancies (13.7 +/- 1.4 and 15.6 +/- 2.2 fmol/ml, respectively). Diabetic pregnancies complicated by gestational hypertension showed lower (p < 0.05) amniotic fluid adrenomedullin concentrations than normotensive diabetic patients. These findings suggest that placental adrenomedullin production is upregulated in diabetic pregnancy, and it may be important to prevent excessive vasoconstriction of placental vessels.     

Perinatal mortality and adverse pregnancy outcomes in a low‐income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low‐income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

Perinatal mortality and adverse pregnancy outcomes in a low-income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low-income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention.     

Growth of the fetus in the abdominal cavity

The ratio pelvic/abdominal cavity is 6.9% in samples of nonhuman mammals and nonhuman primates, and rises to approximately 30% in humans. This relative reduction of the abdomen and increase of the pelvis is associated with a partial or total shift of some organs from the abdomen to the pelvis: rectosigmoid colon, bladder, and genital organs, which are mostly abdominal in quadrupeds and are mostly pelvic in humans. Pregnancy, always abdominal in nonhumans, is pelvic during the first trimester and becomes abdominal later on in humans. Near term the pregnancy expands easily in nonhumans in view of relatively small fetus and relatively large abdominal cavity. But, for the opposite reasons (large fetus, small abdomen), the human pregnancy is limited space-wise during its abdominal expansion. Unlike that of nonhumans, human pregnancy is faced with multiple problems. These include: 1) “squeezing” between the anterior abdominal wall and the lordosis of the lumbar spine; 2) compression of the aortocaval vessels; and 3) forward expansion of the abdomen resulting in reorientation of the trunk during erect posture as the pregnant woman approaches term. All these conditions are responsible for numerous pathological entities that occur during human pregnancy and are almost unknown in nonhuman mammals. © 1993 Wiley-Liss, Inc.     

Isoprostanes, prostaglandins and tocopherols in pre-eclampsia, normal pregnancy and non-pregnancy

This study is designed to evaluate whether oxidative stress and inflammation are involved in severe pre-eclampsia compared to normal pregnancy and non-pregnancy. We have measured plasma and urinary levels of 8-iso-PGF2alpha, a major isoprostane as an indicator of oxidative stress; plasma and urinary 15-keto-dihydro-PGF2alpha, a major metabolite of cyclooxygenase-catalysed PGF2alpha as an indicator of inflammatory response, and plasma -alpha-and -gamma-tocopherol in 18 pre-eclamptic, 19 normal pregnancy and 20 non-pregnant women. Pregnant women had significantly higher levels of 8-iso-PGF2alpha and PGF2alpha metabolite as compared to the non-pregnancy. Levels of 8-iso-PGF2alpha in the pre-eclamptic women did not differ from the normal pregnancy but PGF2alpha metabolite levels were significantly higher in normal pregnancy. On the other hand, gamma-tocopherol levels were significantly lower in pre-eclampsia than normal pregnancy. In contrast, the concentration of alpha-tocopherol was very similar between the groups. alpha-and gamma-tocopherol levels were significantly lower in pregnancy compared to non-pregnancy. Although no direct evidence of oxidative stress and inflammatory response was observed in severe pre-eclampsia, a reduction of gamma-tocopherol suggests the possible precedence of oxidative stress in this condition. Higher levels of isoprostanes and prostaglandin metabolite in late pregnancy suggest the importance of both free radicals and cyclooxygenase-catalysed oxidation products in normal biological processes of pregnancy.     

Effect of maternal weight, adipokines, glucose intolerance and lipids on infant birth weight among women without gestational diabetes mellitus

Background:

The delivery of excess maternal nutrients to the fetus is known to increase the risk of macrosomia, even among infants of women without gestational diabetes mellitus. With the current obesity epidemic, maternal adiposity and its associated effects on circulating adipokines and inflammatory proteins may now have a greater impact on fetal growth. We sought to evaluate the independent effects of maternal glycemia, lipids, obesity, adipokines and inflammation on infant birth weight.

Methods:

We included 472 women who underwent an oral glucose tolerance test in late pregnancy and were found not to have gestational diabetes; 104 (22.0%) had gestational impaired glucose tolerance. We also measured fasting levels of insulin, low-and high-density lipoprotein cholesterol, triglycerides, leptin, adiponectin and C-reactive protein. Obstetric outcomes were assessed at delivery.

Results:

The mean birth weight was 3481 g (standard deviation 493 g); 68 of the infants were large for gestational age. On multiple linear regression analysis, positive determinants of birth weight were length of gestation, male infant, weight gain during pregnancy up to the time of the oral glucose tolerance test, body mass index (BMI) before pregnancy and impaired glucose tolerance in pregnancy. Leptin, adiponectin and C-reactive protein levels were each negatively associated with birth weight. On logistic regression analysis, the significant metabolic predictors of having a large-for-gestational-age infant were BMI before pregnancy (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05–1.27, per 1 kg/m² increase), weight gain during pregnancy up to the time of the oral glucose tolerance test (OR 1.12, 95% CI 1.05–1.19, per 1 kg increase) and leptin level (OR 0.50, 95% CI 0.30–0.82, per 1 standard deviation change).

Interpretation:

Among women without gestational diabetes, maternal adiposity and leptin levels were the strongest metabolic determinants of having a large-for-gestational-age infant rather than glucose intolerance and lipid levels.In 1952, Jørgen Pedersen proposed that delivery of excess maternal glucose to the fetus may be responsible for the increased risk of macrosomia among infants of women with diabetes during pregnancy.¹ He postulated that maternal hyperglycemia leads to fetal hyperglycemia, which in turn stimulates insulin secretion in the fetus, the anabolic effects of which result in excessive fetal growth. Since its introduction, the Pedersen hypothesis has been further extended by other investigators and accepted as the pathophysiologic basis for increased risk of macrosomia among infants of women with diabetes during pregnancy.^2,3 Accordingly, for pregnant women with either pre-existing diabetes or gestational diabetes, modern clinical practice focuses on normalizing blood glucose levels to reduce the risk of fetal hyperglycemia and hence the risk of fetal macrosomia and its associated adverse clinical outcomes (e.g., shoulder dystocia, birth injury, need for cesarean delivery).It is now recognized that the association between maternal nutrients and fetal growth is not restricted solely to women with diabetes. Several studies have shown associations linking maternal blood glucose and triglyceride levels with infant birth weight among women without gestational diabetes.^4–7 This awareness has led to recent recommendations to lower the diagnostic thresholds for gestational diabetes on glucose tolerance testing in pregnancy, to optimize the detection of women who may be at risk of having a large-for-gestational-age infant.⁸Another important factor relevant to the risk of macrosomia is maternal adiposity.⁹ Indeed, the past decade has seen a marked increase in the prevalence of pre-existing obesity among pregnant women.¹⁰ In the context of the current obesity epidemic, we hypothesized that, in women without gestational diabetes, maternal adiposity and its associated effects on circulating levels of adipokines (e.g., adiponectin and leptin) and inflammatory proteins (C-reactive protein) may now have a greater impact than glucose and lipid levels on fetal growth. We conducted this study to evaluate the independent effects of maternal glycemia, lipid levels, obesity, adipokine levels and inflammation on the infant birth weight in a cohort of women without gestational diabetes.     

Leptin in pregnancy: an update

Leptin influences satiety, adiposity, and metabolism and is associated with mechanisms regulating puberty onset, fertility, and pregnancy in various species. Maternal hyperleptinemia is a hallmark of mammalian pregnancy, although both the roles of leptin and the mechanisms regulating its synthesis appear to be taxa specific. In pregnant humans and nonhuman primates, leptin is produced by both maternal and fetal adipose tissues, as well as by the placental trophoblast. Specific receptors in the uterine endometrium, trophoblast, and fetus facilitate direct effects of the polypeptide on implantation, placental endocrine function, and conceptus development. A soluble isoform of the receptor may be responsible for inducing maternal leptin resistance during pregnancy and/or may facilitate the transplacental passage of leptin for the purpose of directly regulating fetal development. The steroid hormones are linked to the regulation of leptin and the leptin receptor and probably interact with other pregnancy-specific, serum-borne factors to regulate leptin dynamics during pregnancy. In addition to its effects on normal conceptus development, leptin is linked to mechanisms affecting a diverse array of pregnancy-specific pathologies that include preeclampsia, gestational diabetes, and intrauterine growth restriction. Association with these anomalies and with mechanisms pointing to a fetal origin for a range of conditions affecting the individual's health in adult life, such as obesity, diabetes mellitus, and cardiovascular disease, reiterate the need for continued research dedicated to elucidating leptin's roles and regulation throughout gestation.     

Outcome of pregnancy in underweight women after spontaneous and induced ovulation

Low maternal weight before pregnancy and poor weight gain during pregnancy are known to result in an increased prevalence of low birthweight infants. Low body weight is also an important cause of amenorrhoea. The hypothesis that amenorrhoeic underweight women who become pregnant after induction of ovulation are more at risk of delivering low birthweight infants than underweight women who ovulate spontaneously was investigated. Forty one pregnant women in whom ovulation had been induced and 1212 in whom ovulation was spontaneous were studied. Women ovulating spontaneously whose weight was normal and who showed good weight gain during pregnancy (>450 g a week) had the lowest incidence (6%) of babies who were small for gestational age. Underweight women (body mass index <19·1) who ovulated spontaneously had a threefold increased risk of delivering babies who were small for gestational age (18%). Overall, the women in whom ovulation had been induced had an even higher risk of babies who were small for dates (25%), and this risk was greatest (54%) in those who were underweight.The outcome of pregnancy is related to weight before conception, which in many cases reflects nutritional state; lack of spontaneous ovulation indicates an increased risk of producing a small for dates infant. The most suitable treatment for infertility secondary to weight related amenorrhoea is therefore dietary rather than induction of ovulation.     

Pregnancy complications among women born preterm

Background:

Adults who were born with low birth weights are at increased risk of cardiovascular and metabolic conditions, including pregnancy complications. Low birth weight can result from intrauterine growth restriction, preterm birth or both. We examined the relation between preterm birth and pregnancy complications later in life.

Methods:

We conducted a population-based cohort study in the province of Quebec involving 7405 women born preterm (554 < 32 weeks, 6851 at 32–36 weeks) and a matched cohort of 16 714 born at term between 1976 and 1995 who had a live birth or stillbirth between 1987 and 2008. The primary outcome measures were pregnancy complications (gestational diabetes, gestational hypertension, and preeclampsia or eclampsia).

Results:

Overall, 19.9% of women born at less than 32 weeks, 13.2% born at 32–36 weeks and 11.7% born at term had at least 1 pregnancy complication at least once during the study period (p < 0.001). Women born small for gestational age (both term and preterm) had increased odds of having at least 1 pregnancy complication compared with women born at term and at appropriate weight for gestational age. After adjustment for various factors, including birth weight for gestational age, the odds of pregnancy complications associated with preterm birth was elevated by 1.95-fold (95% confidence interval [CI] 1.54–2.47) among women born before 32 weeks’ gestation and 1.14-fold (95% CI 1.03–1.25) among those born at 32–36 weeks’ gestation relative to women born at term.

Interpretation:

Being born preterm, in addition to, and independent of, being small for gestational age, was associated with a significantly increased risk of later having pregnancy complications.Numerous studies examining cohorts born mostly in the first half of the 20th century have emphasized the inverse relation between low birth weight and incidence later in life of cardiovascular and metabolic conditions, such as hypertension and type 2 diabetes.¹ Epidemiologic studies seldom consider the effects of preterm birth and intrauterine growth restriction separately when studying the relation of these factors to low birth weight. Studies have suggested that adolescents and young adults born preterm have higher incidence of risk factors for metabolic (insulin resistance) and cardiovascular (higher blood pressure) dysfunctions.^2–4 With the increased survival of preterm newborns over the past 30 years, a substantially greater proportion of young adults are born before 37 or even 32 weeks’ gestation and thus may represent a growing population at risk for conditions related to metabolic syndrome as they get older.Pregnancy can be considered a stress test for future cardiovascular and metabolic health. Women with a history of gestational diabetes, gestational hypertension or preeclampsia are at increased risk of metabolic syndrome later in life.^5–7 Furthermore, studies have shown that women born with low birth weights are at increased risk of gestational hypertension, preeclampsia and gestational diabetes.^8–10 However, many of these studies either have not taken into account gestational age or have a number of shortcomings, such as small sample, young population (mostly teenagers), degree of prematurity not specified or study population consisting mostly of late preterm births.^6,11,12In the province of Quebec, weight and gestational age have been recorded in a registry for all births since 1976, and data on all hospital-based diagnoses have been collected since 1987. The aim of our study was to examine the relation between preterm birth and later pregnancy complications, independently of intrauterine growth restriction, among women born preterm in Quebec between 1976 and 1995 who delivered at least 1 newborn between 1987 and 2008. We also examined whether this association represents a dose–response relation, namely, whether the more prematurely born a woman is, the greater her risk of gestational diabetes, gestational hypertension, preeclampsia or eclampsia.     

Plasmatic regulation of vascular prostacyclin in pregnancy.

Activity of prostacyclin-stimulating factor was measured in six normal, non-pregnant women, six women in early normal pregnancy, six in late normal pregnancy, and six in late pregnancy complicated by severe pre-eclampsia. The activity was lower in the women in late pregnancy than in those in early pregnancy and the controls but was about normal in those with severe pre-eclampsia. These results may be relevant to the physiology of pregnancy and the pathogenesis of pre-eclampsia.     

Low prevalence of glucokinase gene mutations in gestational diabetic patients with good glycemic control

Glucokinase (GCK) plays a key role in glucose homeostasis. Gestational diabetes mellitus increases the risk of gestational complications in pregnant women and fetuses. We screened for mutations in coding and flanking regions of the GCK gene in pregnant women with or without gestational diabetes in a Brazilian population. A sample of 200 pregnant women classified as healthy (control, N = 100) or with gestational diabetes (N = 100) was analyzed for mutations in the GCK gene. All gestational diabetes mellitus patients had good glycemic control maintained by diet alone and no complications during pregnancy. Mutations were detected by single-strand conformation polymorphism and DNA sequencing. Thirteen of the 200 subjects had GCK gene mutations. The mutations detected were in intron 3 (c.43331A>G, new), intron 6 (c.47702T>C, rs2268574), intron 9 (c.48935C>T, rs2908274), and exon 10 (c.49620G>A, rs13306388). None of these GCK mutations were found to be significantly associated with gestational diabetes mellitus. In summary, we report a low frequency of GCK mutations in a pregnant Brazilian population and describe a new intronic variation (c.43331A>G, intron 3). We conclude that mutations in GCK introns and in non-translatable regions of the GCK gene do not affect glycemic control and are not correlated with gestational diabetes mellitus.     

Morbid obesity: Pregnancy risks, birth risks and status of the newborn

In perinatal medicine, severe obesity of the mother occurs in approximately 1% of cases. This is a problem of increasing importance because of the rising prevalence of juvenile obesity. Our retrospective cohort study aimed at characterising high-risk pregnancies associated with morbid obesity (body mass index [BMI]≥40). This is of interest not only from an epidemiological perspective and for developing guidelines for clinical care but also from an anthropological point of view.We analysed the German perinatal statistics of the years 1998-2000 with data from more than 500,000 pregnancies. Pregnant women with coexistent morbid obesity were compared to a normal weight reference sample with regard to gestational, perinatal and neonatal risks. Birth weight percentiles were used to classify the neonates according to size (hypotrophy if <10th, hypertrophy/foetal macrosomia if >90th).The obtained risk profile for morbidly obese pregnant women primarily showed pregnancy related diseases, such as hypertension, pre-eclampsia and gestational diabetes. Hypertension and signs of foetal hypoxaemia occurred at higher frequencies with morbid obesity.Hypertrophic neonates were born 3.3 times more often to obese mothers than to mothers of the normal weight. At a BMI≥40 the rates of complications such as pre-eclampsia, gestational diabetes, impending foetal hypoxaemia, foetal macrosomia, as well as neonatal infections and hyperbilirubinaemia were significantly higher. Obesity and maternal comorbidities, accounted for a higher rate of caesarean sections of up to 38.4% at a BMI≥45. All differences were highly significant.Preconceptionally, the therapeutic approach should be weight reduction.     

Plasma S1P and Sphingosine are not Different Prior to Pre-Eclampsia in Women at High Risk of Developing the Disease

Sphingolipids like sphingosine-1-phosphate (S1P) have been implicated in the pathophysiology of pre-eclampsia. We hypothesized that plasma S1P would be increased in women at high risk of developing pre-eclampsia who subsequently develop the disease. Low circulating placental growth factor (PlGF) is known to be associated with development of pre-eclampsia; so further, we hypothesized that increased S1P would be associated with concurrently low PlGF. This was a case-control study using stored maternal blood samples from 14 to 24 weeks of pregnancy, collected from 95 women at increased risk of pre-eclampsia. Pregnancy outcome was classified as uncomplicated, preterm pre-eclampsia (<37 weeks), or term pre-eclampsia. Plasma lipids were extracted and analyzed by ultraperformance liquid chromatography coupled to electrospray ionization MS/MS to determine concentrations of S1P and sphingosine. Median plasma S1P was 0.339 nmol/ml, and median sphingosine was 6.77 nmol/l. There were no differences in the plasma concentrations of S1P or sphingosine in women who subsequently developed pre-eclampsia, no effect of gestational age, fetal sex, ethnicity, or the presence of pre-existing hypertension. There was a correlation between S1P and sphingosine plasma concentration (P < 0.0001). There was no relationship between S1P or sphingosine with PlGF. Previous studies have suggested that plasma S1P may be a biomarker of pre-eclampsia. In our larger study, we failed to demonstrate there are women at high risk of developing the disease. We did not show a relationship with known biomarkers of the disease, suggesting that S1P is unlikely to be a useful predictor of the development of pre-eclampsia later in pregnancy.