Antepartum fetal surveillance and timing of delivery in the pregnancy complicated by diabetes mellitus

Pregnancies complicated by diabetes mellitus are associated with an increased risk of fetal and neonatal risks compared with pregnancies in the healthy gravida. Data suggest that stillbirth and perinatal mortality may be increased as much as 5 times for patients with insulin-dependent diabetes than in the general population. Pregnancies complicated by preexisting diabetes should undergo twice weekly surveillance with nonstress test or biophysical profile or a combination of both. Doppler studies should be reserved for those patients with vascular disease, intrauterine growth restriction, or hypertensive disorders.     

Maternal medical disease: risk of antepartum fetal death

Although certain maternal medical conditions increase the risk of antepartum fetal death, improvements in medical and obstetric care have decreased the likelihood of stillbirth. This article examines the current stillbirth rates reported in pregnancies complicated by common medical diseases. The reported stillbirth rates are expressed as the number of stillbirths occurring at > or = 20 weeks of gestation per 1,000 births in patients with the condition. Overall, about 10% of all fetal deaths are related to maternal medical illnesses such as hypertension, diabetes, obesity, systemic lupus erythematosus, chronic renal disease, thyroid disorders, and cholestasis of pregnancy. The early recognition of maternal medical diseases provides an opportunity for increased surveillance and interventions that may lead to more favorable pregnancy outcomes.     

Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction

OBJECTIVE: The purpose of this study was to determine whether second-trimester plasma homocysteine levels are elevated among women whose pregnancies are subsequently complicated by pregnancy-induced hypertension, preeclampsia, or intrauterine growth restriction. STUDY DESIGN: Women with normal but relatively low plasma zinc levels were randomly assigned to receive zinc supplementation or placebo from 19 weeks' gestation until delivery. Plasma homocysteine concentration and plasma and erythrocyte folate levels were determined for all available stored samples (zinc group, 231/294; placebo group, 206/286) at 26 and 37 weeks' gestation. Among all women with available samples, pregnancy-induced hypertension (n = 12) or preeclampsia (n = 4) developed in 16 women, and 22 pregnancies were complicated by intrauterine growth restriction. RESULTS: Mean homocysteine levels in women with pregnancy-induced hypertension and preeclampsia were similar to those of control subjects at 26 weeks' gestation but were significantly higher at 37 weeks' gestation. Homocysteine levels were similar between women with pregnancies complicated by intrauterine growth restriction and control subjects at both time points. CONCLUSION: Second-trimester plasma homocysteine concentrations do not predict the subsequent development of pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction.     

Indications for induction of labour: a best-evidence review

Background  Rates of labour induction are increasing.
Objectives  To review the evidence supporting indications for induction.
Search strategy  We listed indications for labour induction and then reviewed the evidence. We searched MEDLINE and the Cochrane Library between 1980 and April 2008 using several terms and combinations, including induction of labour, premature rupture of membranes, post-term pregnancy, preterm prelabour rupture of membranes (PROM), multiple gestation, suspected macrosomia, diabetes, gestational diabetes mellitus, cardiac disease, fetal anomalies, systemic lupus erythematosis, oligohydramnios, alloimmunization, rhesus disease, intrahepatic cholestasis of pregnancy (IHCP), and intrauterine growth restriction (IUGR). We performed a review of the literature supporting each indication.
Selection criteria  We identified 1387 abstracts and reviewed 418 full text articles. We preferentially included high-quality systematic reviews or large randomised trials. Where no such studies existed, we included the best evidence available from smaller randomised trials and observational studies.
Main results  We included 34 full text articles. For each indication, we assigned levels of evidence and grades of recommendation based upon the GRADE system. Recommendations for induction of labour for post-term gestation, PROM at term, and premature rupture of membranes near term with pulmonary maturity are supported by the evidence. Induction for IUGR before term reduces intrauterine fetal death, but increases caesarean deliveries and neonatal deaths. Evidence is insufficient to support induction for women with insulin-requiring diabetes, twin gestation, fetal macrosomia, oligohydramnios, cholestasis of pregnancy, maternal cardiac disease and fetal gastroschisis.
Authors' conclusions  Research is needed to determine risks and benefits of induction for many commonly advocated clinical indications.     

Lupus and pregnancy

Systemic lupus erythematosus (SLE) disproportionately affects women in their reproductive age years. Pregnancy in this systemic autoimmune disease has long been associated with poor obstetric outcomes. However, the frequency of pregnancy loss in lupus has dropped to a level commensurate with that of the general US population. The outcomes of lupus pregnancies are better if conception is delayed until the disease has been inactive for at least 6 months, and the medication regimen has been adjusted in advance. Pregnancy in lupus is prone to complications, including flares of disease activity during pregnancy or in the postpartum period, preeclampsia, miscarriage, stillbirth, intrauterine growth retardation, and preterm birth. Active lupus nephritis poses the greatest risk. The recognition of a lupus flare during pregnancy may be difficult because the signs and symptoms may mimic those of normal pregnancy. Monitoring should include baseline and monthly laboratory tests, serial ultrasonography, fetal surveillance tests, and fetal m-mode echocardiography for mothers with SS-A (Ro) or SS-B (La) antibodies. In the absence of any signs or symptoms of active SLE, affected patients require no specific treatment during pregnancy. If hydroxychloroquine was in use before conception, it should be maintained throughout pregnancy. If a woman with SLE has antiphospholipid antibodies, prophylactic treatment with aspirin and/or low-molecular weight heparin is indicated to prevent fetal loss. Lupus flares during pregnancy are generally treated with hydroxychloroquine, low-dose prednisone, pulse intravenous methylprednisolone, and azathioprine. High-dose prednisone and cyclophosphamide are reserved for severe lupus complications but are associated with significant pregnancy-related complications and poor obstetrical outcomes.     

死胎病因及管理

死胎的主要原因包括妊娠前母体疾病,如糖尿病,以及妊娠期并发症,如产前出血、妊娠期肝内胆汁淤积症、胎儿生长受限、单绒毛膜双胎、感染等。脐动脉彩色超声多普勒有助于预测死胎病因。小剂量阿司匹林（60～80 mg）有助于预防高危妊娠孕妇发生子痫前期及其他不良围生期结局。死胎尸检、胎盘病理检查和胎母出血检测等是死胎病因检查的基本手段。     

Antenatal assessment of the growth restricted fetus

Babies who are small due to intrauterine growth restriction are at higher risk for poor perinatal and long-term outcome than those who are appropriately grown. Through multiple antenatal testing modalities a sequence of deteriorating fetal status can be documented in such cases. The nature of this compromise is best reflected by the combination of fetal biometry, biophysical profile scoring and arterial and venous Doppler. This combination accurately defines fetal states and therefore risk of stillbirth or poor transition to extrauterine life. In the preterm neonate, fetal factors, gestational age and neonatal course interact significantly to impact on short- and long-term outcomes. The potential for iatrogenic prematurity is great and ongoing appraisal of peripartum management is critical. An integrated management protocol accounting for these factors is examined in this review.     

First trimester sex hormone-binding globulin and subsequent development of preeclampsia or other adverse pregnancy outcomes.

OBJECTIVE: To investigate whether first trimester maternal serum sex hormone-binding globulin (SHBG) concentrations are altered in women who subsequently develop preeclampsia or other pregnancy complications. POPULATION: Women undergoing first trimester combined ultrasound and biochemical screening for chromosomal anomalies. We searched the database and identified 32 pregnancies resulting in miscarriage, 64 pregnancies with preexisting or gestational diabetes mellitus, 107 with fetal growth restriction, 103 with preeclampsia, 64 with pregnancy-induced hypertension, and 26 with spontaneous preterm delivery. We also selected 400 controls from among the population of pregnancies that had a delivery of a normal baby with no pregnancy complications. METHODS: Maternal serum SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. The levels between those with normal outcome and those resulting in adverse outcome were compared. RESULTS: The median maternal serum SHBG concentration was not significantly different from controls, in those that subsequently developed preeclampsia (median MoM 1.05), non-proteinuric hypertension (median MoM 0.94) or preterm delivery (median MoM 1.15). The levels were significantly lower in those with diabetes (median MoM, 0.81 p=0.0005) and those pregnancies resulting in miscarriage (median MoM 0.80, p=0.008). CONCLUSION: First trimester maternal serum SHBG concentrations are no different from controls in women who subsequently develop preeclampsia, pregnancy-induced hypertension, fetal growth restriction, or preterm delivery. Levels are reduced in those who subsequently miscarry or in those presenting with diabetes.     

Antiphospholipid Antibodies in Pregnancy

We assessed the relationship between antiphospholipid antibodies and recurrent miscarriage, fetal deaths, and the pregnancy complications--placental abruption, fetal growth retardation and preeclampsia. The subjects were 81 women with a history of 3 or more miscarriages, 62 with a history of fetal death in the index pregnancy, 105 with a poor obstetric history or pregnancy complications and 13 with systemic lupus erythematosus. Antiphospholipid antibodies were found in 41% of women with a history of recurrent miscarriages, 29% with a history of recent intermediate fetal death or stillbirth, 19% with a poor obstetric history and 69% with systemic lupus erythematosus. There is a high incidence of antiphospholipid antibodies in complicated pregnancies. Patients presenting with the above pregnancy disorders should be tested for antiphospholipid antibodies because of the risk conferred on a fetus by their presence and to expand the treatment options.     

Plasma levels of vitamin E in pregnant women prior to the development of preeclampsia and other hypertensive complications

Our aim was to investigate whether decreased levels of vitamin E can be measured during the early stages of pregnancy in women at risk of developing preeclampsia or other associated complications before the onset of the clinical syndrome. We prospectively measured the plasma concentrations of vitamin E in 62 pregnant women at 7-32 weeks of gestation who were at risk of developing preeclampsia and other complications, before the appearance of clinical signs. The results were compared with those of 16 healthy controls. Of the 62 study patients, 8 (13%) developed preeclampsia, and 18 (29%) had other complications, such as intrauterine growth restriction (n = 8), fetal or neonatal loss (n = 9), and preterm delivery (< or = 30 weeks of gestation; n = 7). Both gestational age at delivery and birth weight were significantly lower in the patients with complications than in the healthy controls. However, there were no significant differences in vitamin E levels between women who developed preeclampsia or other complications and those who did not. There was no significant correlation between plasma vitamin E and creatinine concentrations. A significant positive correlation was found in both the complicated and normal pregnancies between plasma vitamin E concentration and gestational week of blood collection (R = 0.485, p < 0.001, and R = 0.718, p = 0.004, respectively). We conclude that the vitamin E concentrations are not decreased prior to the development of preeclampsia or other complications in women at risk.     

Maternal neutrophil apoptosis in normal pregnancy, preeclampsia, and normotensive intrauterine growth restriction.

OBJECTIVE: In normal pregnancy there is both a neutrophilia and a mild neutrophil activation. In preeclampsia both direct and indirect evidence supports further marked neutrophil activation. In the pathogenesis of preeclampsia peripheral blood neutrophils may play a vital role in communicating between the preeclamptic placenta and the maternal vascular endothelium and contribute to the endothelial cell dysfunction that characterizes the maternal syndrome of preeclampsia. Preeclampsia shares many elements with the systemic inflammatory response syndrome. Neutrophils, key effectors of the systemic inflammatory response syndrome, are associated with hepatic necrosis and adult respiratory distress syndrome, both of which most commonly kill women with preeclampsia. We hypothesized that delayed neutrophil apoptosis could explain (1) the neutrophilia of normal pregnancy and (2) the differential maternal responses to the shared placental abnormality of preeclampsia and normotensive intrauterine growth restriction. STUDY DESIGN: Neutrophils were isolated (dextran 500, Ficoll [Amersham Pharmacia Biotech AB, Uppsala, Sweden], and erythrocyte lysis) from (1) case patients with preeclampsia at 相似文献   

Pregnancy outcomes in healthy nulliparas who developed hypertension. Calcium for Preeclampsia Prevention Study Group

OBJECTIVE: To determine maternal and perinatal outcomes in nulliparas with pregnancy-associated hypertension or preeclampsia. METHODS: We conducted (and reported elsewhere) a randomized, double-masked, placebo-controlled trial calcium supplementation of 4589 healthy nulliparas assigned at 13-21 weeks' gestation. This well-defined and characterized data set provided an opportunity to detail more precisely adverse maternal, fetal, and newborn outcomes in women who developed hypertension among a prospective series of healthy nulliparas. RESULTS: Of 4302 women observed to or beyond 20 weeks' gestation, 1073 (24.9%) developed mild or severe pregnancy-associated hypertension or preeclampsia. One hundred sixteen women of the 1073 with hypertension (10.8%) and 336 of the 3229 without hypertension (10.4%) were delivered before 37 weeks' gestation. Fetal and neonatal mortality were similar in those groups; however, selected maternal and newborn morbidities were significantly greater in women with hypertension. Significantly increased maternal morbidities included increased cesarean deliveries, abruptio placentae, and acute renal dysfunction; and significantly increased perinatal morbidities included respiratory distress syndrome, ventilatory support, and fetal growth restriction. Adverse outcomes were highest in women with severe pregnancy-associated hypertension or preeclampsia. CONCLUSION: Hypertension, especially severe hypertension, was associated with an appreciable increase in important maternal and perinatal morbidity but not perinatal mortality.     

Fetal surveillance in pregnancies complicated by insulin-dependent diabetes mellitus.

OBJECTIVE: Our objective was to determine whether maternal vascular disease and/or glycemic control can be related to tests of fetal condition in diabetic pregnancies. STUDY DESIGN: A total of 114 women with insulin-dependent diabetes who used a memory-based glucose reflectance meter were prospectively evaluated. Nonstress testing was begun weekly at 28 to 30 weeks and twice weekly at 32 weeks. A nonreactive nonstress test was followed by a biophysical profile in all cases. RESULTS: A total of 1676 nonstress tests was performed (14.7 +/- 3.2 tests per patient). Eight percent (n = 134) were nonreactive, necessitating a biophysical profile. A comparison of ambulatory glucose profile data, including mean blood glucose level, variation, and excursions from the median, revealed no significant differences in patients with reactive versus nonreactive nonstress tests. Ten patients, including eight with vascular disease, were delivered because of abnormal test results of fetal condition. Nephropathy or hypertension was associated with intervention for fetal well-being in 8 of 20 women (40%) with these risk factors. Only 2 of 94 patients (2%) without nephropathy or hypertension required delivery because of abnormal results of fetal testing (p less than 0.001). One fetal death occurred. No significant differences in the various glycemic parameters were found in women delivered for suspected fetal jeopardy versus the nonintervention group. CONCLUSION: Pregnancies complicated by vascular disease are at greatest risk for abnormal results of fetal testing that necessitate early delivery. Women without vascular complications and with maintenance of good glycemic control rarely have fetal compromise.     

Fetal gastroschisis: a report of 2 cases

BACKGROUND: The risk of stillbirth in fetuses diagnosed with gastroschisis may range from 6% to 12%. Currently there is no agreement on the role of antepartum fetal surveillance, as fetal death within days of reassuring antepartum fetal testing has been reported. CASES: In 2 cases of fetal gastroschisis, fetal gastric distension was associated with decreased fetal movements and nonreactive nonstress tests. Despite reassuring biophysical profile and normal umbilical artery Doppler sonograms, 1 fetus underwent intrauterine death. CONCLUSION: Poor prognostic factors in fetal gastroschisis may include a new finding of persistent fetal gastric distension in association with decreased fetal movements or a nonreactive nonstress test.     

Systemic Lupus Erythematosus in Pregnancy

systemic lupus erythematosus (SLE) in pregnancy is associated with increased maternal and fetal morbidity including fetal loss, growth restriction, and maternal hypertension. Pregnancy complications are more frequent and more severe when conception occurs in patients with lupus nephritis or antiphospholipid antibodies, or during a period of active disease. Lupus flares occur in the majority of pregnancies and often involve the renal and haematologis systems. They tend to be mild to moderate and are treatable with medical therapy, primarily glucocorticoids. Neonatal lupus syndrome is a rare complication of maternal SLE. It is associated with transplacental passage of anti-Ro and/or anti-La antibodies, resulting in cutaneous, haematologic, and cardiac manifestations. Cardiac involvement is common in this syndrome, manifesting as complete congenital heart block due to destruction of the fetal conduction system by antibodies. Antepartum steroid use may be useful in treatment or prevention of congenital heart block. With optimal prenatal care and fetal antepartum surveillance, patients with SLE may have successful, although high risk, pregnancies.     

Hyperhomocysteinemia, pregnancy complications, and the timing of investigation

OBJECTIVE: To assess associations between vitamin-dependent homocysteine metabolism and vascular-related pregnancy complications by considering interval between delivery and postpartum investigation and maternal age. METHODS: Case-control study performed at the University Medical Center Nijmegen in the Netherlands. Patients had experienced pregnancy-induced hypertension (n = 37), preeclampsia (n = 144), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 104), recurrent early pregnancy loss (n = 544), abruptio placentae (n = 135), intrauterine growth restriction (n = 144), or intrauterine fetal death (n = 104). Controls comprised 176 women with uncomplicated obstetric histories. Oral methionine loading tests and fasting vitamin profiles were performed more than 6 weeks after delivery. Odds ratios and 95% confidence intervals were calculated after logistic regression analysis. RESULTS: Hyperhomocysteinemia was associated with an approximately 2-fold to 3-fold increased risk for pregnancy-induced hypertension, abruptio placentae, and intrauterine growth restriction. Cobalamin deficiency was associated with HELLP syndrome, abruptio placentae, intrauterine growth restriction, and intrauterine fetal death. Pyridoxal 5-phosphate deficiency increased the risk for pregnancy-induced hypertension 4-fold. These associations lost their significance after adjustment for time interval and maternal age. High red cell folate was associated with a decreased risk for abruptio placentae and intrauterine growth restriction. An increased creatinine concentration was associated with pregnancy-induced hypertension, preeclampsia, HELLP syndrome, and abruptio placentae. CONCLUSION: Hyperhomocysteinemia and vitamin deficiencies are largely determined by the interval between delivery and postpartum investigation and by maternal age. Time interval and maternal age should be considered in the risk estimation for vascular-related pregnancy complications.     

Doppler waveforms in the fetal aorta and umbilical artery in patients with hypertension in pregnancy

Pulsed Doppler ultrasound assessment of blood flow was performed in the fetal aorta and umbilical arteries of 41 patients with hypertension in pregnancy. Patients were grouped according to severity of the hypertension and the presence or absence of chronic hypertension. Doppler abnormalities were seen in two patients with chronic hypertension, both of whom delivered small for gestational age infants. Only one patient with mild to moderate preeclampsia had abnormal aortic Doppler assessment and was also delivered of a small for gestational age infant. The highest number of abnormal Doppler waveforms in both fetal aorta and umbilical artery were found in patients with severe preeclampsia. Abnormalities were detected more frequently in the fetal aorta than in the umbilical artery. Doppler assessment was often abnormal before a nonstress test or biophysical profile. The number of abnormal Doppler values correlated with perinatal outcome in patients with severe preeclampsia.     

Alloimmunization in twin pregnancies

Among 7052 patients studied between 1976 and 1982 in a collaborative project on antepartum fetal heart rate monitoring, 337 patients had a previous stillbirth as a reason for testing. Overall a previous stillbirth history significantly increased the risk of having a positive result on a contraction stress test, primarily among hypertensive patients. Patients with a previous stillbirth also had a significantly higher incidence of respiratory distress syndrome in their neonates attributable to premature intervention for maternal indications (primarily among hypertensive women and patients with clinical intrauterine growth retardation). Low Apgar scores were found to be significantly increased in diabetics with previous stillbirths primarily due to neonates with congenital malformations. Premature intervention by labor induction or cesarean section was more common among patients with a previous stillbirth for both maternal indications and abnormal antepartum fetal heart rate studies. Previous stillbirth would appear therefore to be a significant risk factor primarily when associated with a diagnosis of hypertension or clinical intrauterine growth retardation.     

Sudden fetal death in women with well-controlled, intensively monitored gestational diabetes.

An intensive antepartum monitoring system for women with gestational diabetes mellitus was evaluated over a 5-year period. Early diagnosis and liberal treatment with insulin was concomitantly followed with non-stress testing: weekly from 28 to 34 weeks' gestation and semi-weekly thereafter. Despite maternal euglycemia and satisfactory antepartum assessment, three fetal deaths occurred within 72 hours of reassuring fetal monitoring. Additionally, 24 (7%) fetuses were delivered on the basis of a low biophysical profile score (less than 6) at term. The stillbirth rate for women with gestational diabetes was 7.7/1000, whereas the stillbirth rate for nondiabetic low-risk patients was 4.8/1000. Women with gestational diabetes continue to be in a high-risk category for antepartum fetal death, requiring intensive monitoring with consideration for timely delivery.     

抗磷脂综合征的围产期抗凝治疗

抗磷脂综合征(APS)是一组以弥漫性动静脉血栓形成、病理妊娠和持续性抗磷脂抗体阳性为特征的综合征。APS能增加复发性流产、早产、死产、子痫前期、胎儿生长受限等妊娠并发症的发生率。不利的妊娠结局和妊娠期血栓形成之间有关联。围产期APS的治疗主要是对症治疗、防止再次发生血栓和病理妊娠。低剂量阿司匹林和肝素能改善APS的妊娠结局。