Showing papers on "Pregnancy published in 1996"

Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum

Abstract: Rare nucleated fetal cells circulate within maternal blood. Noninvasive prenatal diagnosis by isolation and genetic analysis of these cells is currently being undertaken. We sought to determine if genetic evidence existed for persistent circulation of fetal cells from prior pregnancies. Venous blood samples were obtained from 32 pregnant women and 8 nonpregnant women who had given birth to males 6 months to 27 years earlier. Mononuclear cells were sorted by flow cytometry using antibodies to CD antigens 3, 4, 5, 19, 23, 34, and 38. DNA within sorted cells, amplified by PCR for Y chromosome sequences, was considered predictive of a male fetus or evidence of persistent male fetal cells. In the 32 pregnancies, male DNA was detected in 13 of 19 women carrying a male fetus. In 4 of 13 pregnancies with female fetuses, male DNA was also detected. All of the 4 women had prior pregnancies; 2 of the 4 had prior males and the other 2 had terminations of pregnancy. In 6 of the 8 nonpregnant women, male DNA was detected in CD34+CD38+ cells, even in a woman who had her last son 27 years prior to blood sampling. Our data demonstrate the continued maternal circulation of fetal CD34+ or CD34+CD38+ cells from a prior pregnancy. The prolonged persistence of fetal progenitor cells may represent a human analogue of the microchimerism described in the mouse and may have significance in development of tolerance of the fetus. Pregnancy may thus establish a long-term, low-grade chimeric state in the human female.

Schizophrenia after prenatal famine. Further evidence.

Abstract: Background: Suggestive findings of an earlier study that prenatal nutritional deficiency was a determinant of schizophrenia prompted us to undertake a second test of the hypothesis using more precise data on both exposure and outcome. Methods: Among persons born in the cities of western Netherlands during 1944 through 1946, we compared the risk for schizophrenia in those exposed and unexposed during early gestation to the Dutch Hunger Winter of 1944/1945. The frequency of hospitalized patients with schizophrenia at age 24 to 48 years in the exposed and unexposed birth cohorts was ascertained from a national psychiatric registry. Results: The most exposed birth cohort, conceived at the height of the famine, showed a twofold and statistically significant increase in the risk for schizophrenia (relative risk [RR] = 2.0; 95% confidence interval [CI] = 1.2 to 3.4;P Conclusion: Prenatal nutritional deficiency may play a role in the origin of some cases of schizophrenia.

Maternal nutrition in early and late pregnancy in relation to placental and fetal growth

Abstract: Objective: To assess how nutrient intakes of mothers in early and late pregnancy influence placental and fetal growth. Design: Prospective observational study. Setting: Princess Anne Maternity Hospital, Southampton. Subjects: 538 mothers who delivered at term. Main outcome measures: Placental and birth weights adjusted for the infant9s sex and duration of gestation. Results: Mothers who had high carbohydrate intakes in early pregnancy had babies with lower placental and birth weights. Low maternal intakes of dairy and meat protein in late pregnancy were also associated with lower placental and birth weights. Placental weight fell by 49 g (95% confidence interval 16 g to 81 g; P=0.002) for each log g increase in intake of carbohydrate in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in intake of dairy protein in late pregnancy. Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy. These associations were independent of the mother9s height and body mass index and of strong relations between the mother9s birth weight and the placental and birth weights of her offspring. Conclusion: These findings suggest that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy. Such an effect could have long term consequences for the offspring9s risk of cardiovascular disease.

Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy.

Abstract: Antigen- and mitogen-stimulated cytokine production by peripheral blood mononuclear cells (PBMC) of 50 pregnant women and 31 age- and sex-matched non-pregnant controls were analysed to determine whether changes in cytokine production occur during normal and pathologic human gestation. The pregnant women, consecutively enrolled during a 3-month period, were undergoing a normal, non-pathologic pregnancy at the time of entry into the study, and underwent ultrasound examination to ascertain the exact week of pregnancy and the vitality of the fetus. Forty of the 50 pregnancies (80%) terminated physiologically with the birth of normal babies. Spontaneous abortions were observed in 5/50 (10%) women, and five women gave birth to newborns small for gestational age (SGA). A decrease in the production of IL-2 and interferon-gamma (IFN-γ) accompanied by an increase in production of IL-4 and IL-10, was observed in normal pregnancy, with the lowest quantities of IL-2 and IFN-γ and the highest quantities of IL-4 and IL-10 present in the third trimester of pregnancy. Statistically significant increased production of both IL-2 and IFN-γ and reduced production of IL-10 characterized pathologic pregnancies and distinguished them from normal pregnancies. These preliminary data suggest that a type 2 cytokine profile may be associated with normal human pregnancy, whereas the lack of a dominant type 2 cytokine profile may be indicative of a pathologic pregnancy.

Pregnancy and the Risk of Stroke

Abstract: Background It is widely believed that pregnancy increases the risk of stroke, but there are few data available to quantify that risk. Methods We identified all female patients 15 through 44 years of age in central Maryland and Washington, D.C., who were discharged from any of 46 hospitals in the study area in 1988 or 1991. Two neurologists reviewed each case, using data from the women's medical records. We determined whether the women had been pregnant at the time of the stroke or up to six weeks before it occurred. For purposes of this analysis, the six-week period after pregnancy could begin with an induced or spontaneous abortion or with the delivery of a live or stillborn child. Results Seventeen cerebral infarctions and 14 intracerebral hemorrhages occurred in women who were or had recently been pregnant (pregnancy-related strokes), and there were 175 cerebral infarctions and 48 intracerebral hemorrhages that were not related to pregnancy. For cerebral infarction, the relative risk during pregnancy, ...

Pharmacologic management of psychiatric illness during pregnancy: Dilemmas and guidelines

Abstract: Objective : Given concerns about use of psychotropic medication during pregnancy, the authors reviewed the literature regarding the effects of prenatal exposure to psychotropic medications on fetal outcome. Method : A MEDLINE search of all articles written in English from 1966 to 1995 was performed to review information on the effects of psychotropic drug use during pregnancy on fetal outcome. Where sufficient data were available and when methodologically appropriate, meta-analyses were performed to assess risk of fetal exposure by psychotropic medication class. Results : Three primary effects are associated with medication use during pregnancy : 1) teratogenicity, 2) perinatal syndromes (neonatal toxicity), and 3) postnatal behavioral sequelae. For many drug classes there are substantial data regarding risk for teratogenicity. Tricyclic antidepressants do not seem to confer increased risk for organ dysgenesis. The available data indicate that first-trimester exposure to low-potency phenothiazines, lithium, certain anticonvulsants, and benzodiazepines may increase the relative risk for congenital anomalies. However, the absolute risk of congenital malformations following prenatal exposure to most psychotropics is low. Conclusions : Exposure to certain psychotropic drugs in utero may increase the risk for some specific congenital anomalies, but the rate of occurrence of these anomalies even with the increased risk remains low. Use of psychotropic medications during pregnancy is appropriate in many clinical situations and should include thoughtful weighing of risk of prenatal exposure versus risk of relapse following drug discontinuation. The authors present disorder-based guidelines for psychotropic drug use during pregnancy and for psychiatrically ill women who wish to conceive.

Human aneuploidy: Incidence, origin, and etiology

Abstract: Chromosome abnormalities occur with astonishing frequency in humans, being present in an estimated 1030% of all fertilized eggs. Of the different classes of chromosome abnormality, aneuploidy (trisomy and monosomy) is by far the most common and, clinically, the most important. For example, over 25% of all miscarriages are monosomic or trisomic, making aneuploidy the leading known cause of pregnancy loss. Furthermore, among those conceptions that survive to term, aneuploidy is the leading genetic cause of mental retardation. Over the past 25 years, a considerable body of information has accrued on the incidence of aneuploidy in human gametes, fetuses, and newborns. More recently, the application of molecular biological techniques to the study of aneuploidy has begun to uncover some of the underlying causes of human aneuploidy. In this review, we first summarize the cytogenetic data on the incidence of aneuploidy in humans, and then discuss recent molecular data on the mechanism of origin of different aneuploid conditions, the basis of the maternal age effect on aneuploidy, and the importance of aberrant genetic recombination to the genesis of aneuploidy.

Induction of labor compared with expectant management for prelabor rupture of the membranes at term

Abstract: Background As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. It is not known whether inducing labor will reduce this risk or whether one method of induction is better than another. Methods We studied 5041 women with prelabor rupture of the membranes at term. The women were randomly assigned to induction of labor with intravenous oxytocin; induction of labor with vaginal prostaglandin E2 gel; or expectant management for up to four days, with labor induced with either intravenous oxytocin or vaginal prostaglandin E2 gel if complications developed. The primary outcome was neonatal infection. Secondary outcomes were the need for cesarean section and women's evaluations of their treatment. Results The rates of neonatal infection and cesarean section were not significantly different among the study groups. The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group, 3.0 percent for the induction-with...

Chronic Maternal Undernutrition in the Rat Leads to Delayed Postnatal Growth and Elevated Blood Pressure of Offspring

Abstract: To determine the effects of chronic maternal undernutrition on postnatal somatic growth and blood pressure, pregnant dams were randomly assigned to one of two dietary treatment groups. A control group was fed ad libitum throughout pregnancy and a restricted group was fed 30% of ad libitum intake. From birth, feeding was ad libitum in both groups, and litter size was adjusted to eight pups per litter. Litter size was not significantly altered by the reduced maternal intake. Offspring of the restricted fed group were significantly smaller than offspring from the ad libitum fed group from birth until 12 wk of age, but by 30 wk had similar body weights. Blood pressure was measured by tail cuff plethysmography. Offspring from the restricted fed group were found to have significantly (p < 0.05) elevated systolic blood pressure (5-8 mm Hg) at 30, 48, and 56 wk of age. These data demonstrate that nutritional deprivation in the pregnant rat leads to changes in postnatal allometric growth patterns, to delayed catch-up growth, and to elevated blood pressure in adulthood. The data are consistent with the hypothesis that poor maternal nutrition in pregnancy may irreversibly alter programming of the development of cardiovascular homeostasis.

Is maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children

Abstract: OBJECTIVE This study investigated the role of maternal smoking during pregnancy in the etiology of attention deficit hyperactivity disorder (ADHD). METHOD Subjects were 6-17-year-old boys with DSM-III-R ADHD (N = 140) and normal comparison subjects (N = 120) and their first-degree biological relatives. Information on maternal smoking was obtained from mothers in a standardized manner by raters who were blind to the proband's clinical status. RESULTS Twenty-two percent of the ADHD children had a maternal history of smoking during pregnancy, compared with 8% of the normal subjects. This positive association remained significant after adjustment for socioeconomic status, parental IQ, and parental ADHD status. Significant differences in IQ were found between those children whose mothers smoked during pregnancy and those whose mothers did not smoke (mean IQ = 104.9, SD = 12.3, and mean = 115.4, SD = 12.2, respectively). CONCLUSIONS These findings suggest that maternal smoking during pregnancy is a risk factor for ADHD. If confirmed, these findings will stress the importance of programs aimed at smoking prevention in nonsmoking women and smoking cessation in smoking women of childbearing age.

Organ-selective growth in the offspring of protein-restricted mothers.

Abstract: Recent epidemiological studies in people whose birth weights were recorded many years ago suggest links between impaired growth during early life and the development of diseases, including diabetes, much later in life. The long-term effects of retarded early growth are proposed to result from malnutrition at critical periods of fetal or infant development leading to reduction in the growth of organs and permanent changes in their metabolism or structure, or both. In order to investigate this, a rat model was established which involved feeding either a diet containing 200 g protein/kg or an isoenergetic diet containing 80 g protein/kg to pregnant and lactating rats. In addition, cross-fostering techniques were employed which allowed a separate evaluation of the prenatal or the postnatal periods. The offspring were studied at 21 d of age or were weaned onto a normal laboratory chow and studied at 11 months of age. The 80 g protein/kg diet during pregnancy did not affect the overall reproductive although more subtle differences were evident. Permanent growth retardation was evident in offspring subjected to maternal protein restriction during the postnatal period. At 21 d of age the offspring of protein-restricted mothers exhibited selective changes in organ growth: compared with the body weight, the lung and brain experienced a smaller decrease in weight: the heart, kidney and thymus decreased proportionately: whereas, the pancreas, spleen, muscle and liver showed a greater reduction in weight. In older animals the muscle weight was lower in the male rats and the relative weight of pancreas was increased in the female rats.

T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells.

Abstract: Maternal immune responses can influence fetal survival and several cytokines have harmful or protective effects on pregnancy. The Th1 cytokines IFN-gamma and IL-2 can cause fetal loss, whereas the Th2 cytokine IL-10 is protective. However, infections such as leishmaniasis show the opposite pattern: resistance is associated with the preferential mounting of a Th1 response, whereas a Th2 response exacerbates the disease. We therefore asked whether the curative Th1 response against Leishmania major in genetically resistant C57BL/6 mice, would compromise concurrent pregnancy. The number of resorptions as assessed by uterine scars was significantly increased in infected C57BL/6 mice and this was associated with a decreased production by placental cells of the Th2 cytokines IL-4 and IL-10 and increased production of IFN-gamma and TNF. Interestingly, the frequency of pregnancy failure before implantation in C57BL/6 mice was also substantially increased. In contrast to C57BL/6 mice, early infection did not reduce implantations in BALB/c mice that mount a Th2 anti-L. major response and succumb to infection. For both resorptions and implantations, there appeared to be a short period early in infection that was detrimental to pregnancy, followed by a period with lesser effects, and a later period that again induced higher resorptions or pre-implantation losses. These results suggest that a beneficial anti-parasite Th1 response can adversely affect pregnancy outcome. Furthermore, Th1 cytokines may be deleterious for not only placental maintenance but also preimplantation events.

Outcome of Pregnancy in Women with Moderate or Severe Renal Insufficiency

Abstract: Background Pregnant women with mild preexisting renal disease have relatively few complications of pregnancy, but the risks of maternal and obstetrical complications in women with moderate or severe renal insufficiency remain uncertain. Methods We determined the frequency and types of maternal and obstetrical complications and the outcomes of pregnancy in 67 women with primary renal disease (82 pregnancies). All the women had initial serum creatinine concentrations of at least 1.4 mg per deciliter (124 μmol per liter) and gestations that continued beyond the first trimester. Results The mean (±SD) serum creatinine concentration increased from 1.9±0.8 mg per deciliter (168±71 μmol per liter) in early pregnancy to 2.5±1.3 mg per deciliter (221±115 μmol per liter) in the third trimester. The frequency of hypertension rose from 28 percent at base line to 48 percent in the third trimester, and that of high-grade proteinuria (urinary protein excretion, >3000 mg per liter) from 23 percent to 41 percent. For the ...

Demographic and obstetric risk factors for postnatal psychiatric morbidity

Abstract: BACKGROUND Postnatal depression follows 10% of live births but there is little consensus on the risk factors associated with its development. Previous smaller studies have been unable to quantify the impact of independent risk factors as relative and attributable risks. METHOD The Edinburgh Postnatal Depression Scale (EPDS) was used to screen a systematic sample of 2375 women, six to eight weeks after delivery. Information on socio-demographic and obstetric variables was collected at the screening interview. The risk factors associated with high EPDS scores (> 12) were determined and entered stepwise into a regression model. RESULTS Four independent variables were found to be associated with an EPDS score above this threshold. These were an unplanned pregnancy (OR 1.44); not breast-feeding (OR 1.52), and unemployment in either the mother, i.e. no job to return to following maternity leave (OR 1.56), or the head of household (OR 1.50). These four variables appeared to explain the risk associated with other risk factors. CONCLUSIONS Although a direct aetiological role for these risk factors is not certain, they may indicate strategies for the prevention of affective morbidity in postnatal women. These may include reducing unwanted pregnancy and employment for women after childbirth.

Smoking and the sudden infant death syndrome: results from 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy

Abstract: Objective: To investigate the effects of exposure to tobacco smoke and of parental consumption of alcohol and illegal drugs as risk factors for the sudden infant death syndrome after a national risk reduction campaign which included advice on prenatal and postnatal avoidance of tobacco smoke. Design: Two year population based case-control study. Parental interviews were conducted for each infant who died and four controls matched for age and date of interview. Setting: Three regions in England with a total population of 17 million people. Subjects: 195 babies who died and 780 matched controls. Results: More index than control mothers (62.6% v 25.1%) smoked during pregnancy (multivariate odds ratio = 2.10; 95% confidence interval 1.24 to 3.54). Paternal smoking had an additional independent effect when other factors were controlled for (2.50; 1.48 to 4.22). The risk of death rose with increasing postnatal exposure to tobacco smoke, which had an additive effect among those also exposed to maternal smoking during pregnancy (2.93; 1.56 to 5.48). The population attributable risk was over 61%, which implies that the numbers of deaths from the syndrome could be reduced by almost two third if parents did not smoke. Alcohol use was higher among index than control mothers but was strongly correlated with smoking and on multivariate analysis was not found to have any additional independent effect. Illegal drug use was more common among the index parents, and paternal use of illegal drugs remained significant in the multivariate model (4.68; 1.56 to 14.05). Conclusions: This study confirms the increased risk of the sudden infant death syndrome associated with maternal smoking during pregnancy and shows evidence that household exposure to tobacco smoke has an independent additive effect. Parental drug misuse has an additional small but significant effect. Key messages Exposure of babies to tobacco smoke from other members of the household before or after birth increases the risk of death: the greater the exposure the higher the risk Over 60% of such deaths may be attributable to the effects of exposure to tobacco smoke before and after birth

Treatment of Hypertension in Pregnant Women

Abstract: Hypertensive disorders are the most common medical complications of pregnancy and are an important cause of maternal and perinatal morbidity and mortality worldwide.1 During normal pregnancy, systolic pressure changes little; however, diastolic pressure decreases by an average of 10 mm Hg early in gestation (13 to 20 weeks) and rises again to prepregnancy levels in the third trimester. The term “hypertension in pregnancy” describes a broad spectrum of conditions in which blood pressure varies widely. In reviewing the literature on this subject, one is faced with difficulties regarding the definitions and classifications used to categorize hypertension in pregnant women,2– . . .

Doppler ultralsound of the uterine arteries: the importance of bilateral notching in the prediction of pre-eclampsia, placental abruption or delivery of a small-for-gestational-age baby

Abstract: The use of Doppler studies of the uterine arteries in the prediction of pre-eclampsia and intrauterine growth retardation has had mixed success. The introduction of color Doppler imaging and the use of the "notch' to define an abnormal waveform have helped to improve the predictive value of uterine artery Doppler screening. The aim of this study was to evaluate the use of uterine artery Doppler in a group of women of mixed race and parity. This study was a prospective, cross-sectional analysis of 1326 unselected women who were screened with continuous wave uterine Doppler at 19-21 weeks, as part of a fetal anomaly/dating scan. A total of 214 women with abnormal uterine artery waveforms (notching) were referred for assessment at 24 weeks; 191 attended and had color Doppler imaging/pulsed Doppler studies of both uterine arteries. Data from 185 pregnancies were suitable for analysis. There were abnormal uterine Doppler findings (uni- or bilateral notching) in 110 patients at 24 weeks; 48 had bilateral notching. The sensitivity of notching for the prediction of proteinuric pregnancy-induced hypertension (PPIH) was similar in primiparas (76.9%), multiparas (77.7%), African-Caribbean women (82.6%) and Caucasian women (71.4%). The sensitivity of bilateral notching for the prediction of PPIH requiring delivery before 34 weeks was 81.2%, and 57.6% for babies small for gestational age (SGA), with positive predictive values of 27% (PPIH), 31.2% (SGA) and 37.5% (any complication). Patients with persistent bilateral notching are particularly at risk of developing PPIH or delivering an SGA baby before 34 weeks' gestation; they warrant increased surveillance, and may be a group that could benefit from prophylactic therapies.

Back pain during pregnancy: a prospective study.

Abstract: Study design A longitudinal, prospective, observational, cohort study. Objectives To describe the natural history of back pain occurring during pregnancy and immediately after delivery. Summary of background data Back pain during pregnancy is a frequent clinical problem even during the early stages of pregnancy. The cause is unclear. Methods A cohort of 200 consecutive women attending an antenatal clinic were followed throughout pregnancy with repeated measurements of back pain and possible determinants by questionnaires and physical examinations. Results Seventy-six percent reported back pain at some time during pregnancy. Sixty-one percent reported onset during the present pregnancy. In this group, the prevalence rate increased to 48% until the 24th week and then remained stable and declined to 9.4% after delivery. The reported pain intensity increased by pain duration. The pain score correlated closely to self-rated disability and days of sickness benefit. Conclusions Back pain during pregnancy is a common complaint. The 30% with the highest pain score reported great difficulties with normal activities. The back pain started early in pregnancy and increased over time. Young women had more pain than older women. Back pain starting during pregnancy may be a special entity and may have another origin than back pain not related to pregnancy.

Inhibition of 11β-Hydroxysteroid Dehydrogenase in Pregnant Rats and the Programming of Blood Pressure in the Offspring

Abstract: Recent epidemiological studies have linked low birth weight with the later occurrence of cardiovascular and metabolic disorders, particularly hypertension. We have proposed that fetal exposure to excess maternal glucocorticoids may underpin this association. Normally, the fetus is protected from maternal glucocorticoids by placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD). We have previously shown that treatment of pregnant rats with dexamethasone, a synthetic glucocorticoid that is poorly metabolized by the enzyme, reduces birth weight and produces elevated blood pressure in the adult offspring. Moreover, low activity of placental 11beta-HSD correlates with low birth weight in rats. Here, we show that maternal administration of carbenoxolone, a potent inhibitor of 11 beta-HSD, throughout pregnancy leads to reduced birth weight (mean 20 percent decrease) and elevated blood pressures (increase in mean arterial pressure, 9 mm Hg in males, 7 mm Hg in females) in the adult offspring of carbenoxolone-treated rats. This effect requires the presence of maternal adrenal products, as carbenoxolone given to adrenalectomized pregnant rats had no effect on birth weight or blood pressure. These data support the hypothesis that excess exposure of the fetoplacental unit to maternal glucocorticoids reduces birth weight and programs subsequent hypertension and indicate a key role for placental 11beta-HSD in controlling such exposure.