Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial.

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.

Evidence for cutaneous dysbiosis in dystrophic epidermolysis bullosa.

BACKGROUND: The human microbiome project addresses the relationship between bacterial flora and the human host, in both healthy and diseased conditions. The skin is an ecosystem with multiple niches, each featuring unique physiological conditions and thus hosting different bacterial populations. The skin microbiome has been implicated in the pathogenesis of many dermatoses. Given the role of dysbiosis in the pathogenesis of inflammation, which is prominent in dystrophic epidermolysis bullosa (DEB), we undertook a study on the skin microbiome. AIM: To characterize the skin microbiome in a series of patients with DEB. METHODS: This was a case-control study of eight patients with DEB and nine control cases enrolled between June 2017 and November 2018. The skin of patients with DEB was sampled at three different sites: untreated wound, perilesional skin and normal-appearing (uninvolved) skin. Normal skin on the forearm was sampled from age-matched healthy controls (HCs). We used a dedicated DNA extraction protocol to isolate microbial DNA, which was then analysed using next-generation microbial 16S rRNA sequencing. Data were analysed using a series of advanced bioinformatics tools. RESULTS: The wounds, perilesional and uninvolved skin of patients with DEB demonstrated reduced bacterial diversity compared with HCs, with the flora in DEB wounds being the least diverse. We found an increased prevalence of staphylococci species in the lesional and perilesional skin of patients with DEB, compared with their uninvolved, intact skin. Similarly, the uninvolved skin of patients with DEB displayed increased staphylococcal content and significantly different microbiome diversities (other than staphylococci) compared with HC skin. CONCLUSIONS: These findings suggest the existence of a unique DEB-associated skin microbiome signature, which could be targeted by specific pathogen-directed therapies. Moreover, altering the skin microbiome with increasing colonization of bacteria associated with nonchronic wounds may potentially facilitate wound healing in patients with DEB.

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis.

BACKGROUND: The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. OBJECTIVES: To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. METHODS: Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI-TOF) in a prospective study. RESULTS: Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis. CONCLUSIONS: Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response. What's already known about this topic? Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results. To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria. What does this study add? This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry. The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response. What is the translational message? Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

Routine antenatal ultrasound in low- and middle-income countries: first look - a cluster randomised trial.

OBJECTIVE: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centres in resource-limited countries. DESIGN: Cluster randomised trial. SETTING: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia) METHODS: Clusters were randomised to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality. RESULTS: During the 24-month trial, 28 intervention and 28 control clusters had 24 263 and 23 160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa, and abnormal lie was within expected ranges. 9% were referred for an ultrasound-diagnosed condition, and 71% attended the referral. The ANC (RR 1.0 95% CI 1.00, 1.01) and hospital delivery rates for complicated pregnancies (RR 1.03 95% CI 0.89, 1.20) did not differ between intervention and control clusters nor did the composite outcome (RR 1.09 95% CI 0.97, 1.23) or its individual components. CONCLUSIONS: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome and the individual components were not reduced. TWEETABLE ABSTRACT: Antenatal care ultrasound did not improve a composite outcome that included maternal, fetal, and neonatal mortality.

Prepregnancy Weight in Women with Type I Diabetes Mellitus: Effect on Pregnancy Outcomes.

Objective This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI (< 20 kg/m2), normal BMI (20 to < 25 kg/m2), and high BMI (≥ 25 kg/m2). The outcomes of interest were: spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent delivery for maternal indications (hypertension or placental abruption); and preterm delivery (< 37 weeks gestation). Analyses included proportional hazards and multiple logistic regression models with covariates: age, age at diagnosis of type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or retinopathy), and glycohemoglobin A1 concentrations. Results Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A1 was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI).

Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids.

OBJECTIVE: The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. RESULTS: CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

Characteristics of women with nausea and vomiting of pregnancy who chose to continue compassionate use of placebo after a randomised trial.

The placebo effect has not been characterised in pregnant women suffering from nausea and vomiting of pregnancy (NVP). Our aim was to characterise determinants of the placebo effect in women treated with placebo for NVP. We analysed data from a multicentre, double blind randomised controlled trial of Diclectin (delayed release doxylamine and pyridoxine) vs placebo for the treatment of NVP. A total of 127 women in the placebo arm and 130 in the active arm provided evaluable data for this analysis. Women who chose to continue placebo on a compassionate basis (n = 41) had significantly better improvement in symptoms of NVP and higher Wellbeing scores than those who did not ask to continue compassionate use. Results were similar in the active drug arm. The request to continue compassionate use of either placebo or active drug could be predicted by greater improvement in symptoms of NVP during the trial period.

Preterm prediction study: comparison of the cervical score and Bishop score for prediction of spontaneous preterm delivery.

OBJECTIVE: To prospectively compare digital cervical score with Bishop score as a predictor of spontaneous preterm delivery before 35 weeks of gestation. METHODS: Data from a cohort of 2,916 singleton pregnancies enrolled in a multicenter preterm prediction study were available. Patients underwent digital cervical examinations at 22-24 and 26-29 weeks of gestation for calculation of Bishop score and cervical score. Relationships between Bishop score, cervical score, and spontaneous preterm delivery were assessed with multivariable logistic regression analysis, McNemar test, and receiver operating characteristic (ROC) curves to identify appropriate diagnostic thresholds and predictive capability. RESULTS: One hundred twenty-seven of 2,916 patients (4.4%) undergoing cervical examination at 22-24 weeks had a spontaneous preterm delivery before 35 weeks. Eighty-four of the 2,538 (3.3%) reexamined at 26-29 weeks also had spontaneous preterm delivery. Receiver operating characteristic curves indicated that optimal diagnostic thresholds for Bishop score were at least 4 at 22-24 weeks, at least 5 at 26-29 weeks, and less than 1.5 at both examinations for cervical score. At 22-24 weeks, areas under the ROC curve favored Bishop score. At 26-29 weeks, there was no significant difference in areas under the ROC curve; however, a cervical score less than 1.5 (sensitivity 35.7%, false positive rate 4.8%) was superior to a Bishop score of 5 or more (P<.001). CONCLUSION: Both cervical evaluations are associated with spontaneous preterm delivery in a singleton population; however, predictive capabilities for spontaneous preterm delivery were modest among women with low event prevalence. Although Bishop score performed better in the mid trimester, by 26-29 weeks a cervical score less than 1.5 was a better predictor of spontaneous preterm delivery before 35 weeks than a Bishop score of at least 5.

Deficient counterregulation: a possible risk factor for excessive fetal growth in IDDM pregnancies.

OBJECTIVE: The rate of macrosomia in infants born to women with IDDM remains high despite intensive insulin therapy and good glycemic control. We hypothesized that one of the factors contributing to this high rate of macrosomia is deficient counterregulatory hormonal responses to hypoglycemia. RESEARCH DESIGN AND METHODS: Hypoglycemia was induced in 17 women with IDDM and 10 normal control subjects at 24-28 and at 32-34 weeks' gestation, using the hypoglycemic clamp technique. Plasma glucose concentrations were decreased to 3.3 mmol/l and maintained at this level for 1 h. Blood samples were drawn every 15 min for measurement of counterregulatory hormone concentrations. RESULTS: All 17 women with IDDM had diminished epinephrine responses to hypoglycemia, compared with control subjects. Eight of the women with IDDM (nonresponders) had minimal or no responses (< 165 pmol/l above baseline) and nine women (responders) had a moderate response (244-764 pmol/l). Of the eight nonresponders, seven had large infants (birth weight in the upper quartile), while only three of the nine responders had large infants (P < 0.05). CONCLUSIONS: Severely impaired counterregulatory epinephrine responses to hypoglycemia in pregnant women with IDDM may be a factor contributing to excessive fetal growth. We speculate that in these women, recurrent episodes of hypoglycemia may result in frequent bouts of increased caloric intake, with repeated episodes of transient hyperglycemia leading to fetal hyperinsulinism and excessive fetal growth.

Major malformations in infants of IDDM women. Vasculopathy and early first-trimester poor glycemic control.

From animal and in vitro studies, it has been suggested that high environmental glucose, ketone, or insulin concentrations and low glucose or insulin concentrations may be etiologic factors for congenital malformations (CMs) in infants of diabetic mothers (IDMs). Transplacental passage of antibody-bound insulin has been demonstrated in humans. Controversy exists regarding the pathophysiology of CMs in human insulin-dependent diabetes mellitus (IDDM) pregnancies. We hypothesized that CMs in IDMs are associated with maternal vasculopathy, poor first-trimester glycemic control (i.e., hyper- and/or hypoglycemia), advanced White class, and high insulin requirements. We studied 165 first pregnancies of women with IDDM from 1978 to 1986. The goals of glucose control were a fasting blood glucose of less than 100 mg/dl and a 90-min postprandial blood glucose of less than 140 mg/dl. Insulin requirements, body weight, and pre- and postprandial blood glucose were recorded at weekly clinic visits. Maternal blood HbA1 was measured on entry and every 4 wk to confirm that adequate glycemic control was achieved. Women who enrolled in the project were interviewed during gestation by a geneticist/dysmorphologist who obtained genetic and environmental histories using a standard questionnaire. All live-born infants and stillbirths were examined. Each live-born infant was assessed systematically by two independent examiners, a neonatologist and a geneticist/dysmorphologist; examination with standardized checklists was performed in the newborn nursery as soon after birth as was practical. In first pregnancies in the study, there were 13 IDMs with major CMs (7.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of effect of pregnancy on renal allograft survival or function.

To determine whether pregnancy had a long-term influence on the survival or function of renal allografts, a case-control study was conducted. Patients were selected from a pool of 915 patients transplanted at the University of Cincinnati from 1967 to 1990. The pregnancy group consisted of 18 women who became pregnant 3 months to 17 years after transplantation and who elected to continue pregnancy. There were 26 nonpregnant female controls, and 23 male control renal transplant recipients. Matching criteria were cause of end-stage renal disease (ESRD), donor source, age at transplantation, calendar year of transplantation, time from transplantation to pregnancy, and serum creatinine concentration at the time corresponding to conception. Matching was performed by one investigator, who had no knowledge of long-term outcome in any of the patients. The three groups were well-matched with regard to these criteria. Male controls had higher baseline creatinine clearances than pregnancy cases or female controls. During pregnancy, serum creatinine levels fell by 20%, and creatinine clearance rose by 53%. Immediately after pregnancy, these values returned to baseline. Graft survival, with a mean posttransplant follow-up of 11-12 years, was 77.8% in the pregnancy cases, 69.2% in the female controls, and 69.6% in the male controls. By life-table analysis, none of these differences was significant. Among surviving grafts, serum creatinine levels and creatinine clearances remained stable throughout the follow-up period. In this study, using well-matched male and nonpregnant female cohorts for comparison, pregnancy did not have an adverse long-term effect on renal allograft function or survival.

Macrosomia in infants of insulin-dependent diabetic mothers.

The purpose of the present study was to evaluate factors affecting the rate of macrosomia and related complications in a population of infants of insulin-dependent diabetic mothers. The following factors were hypothesized to be predisposing to macrosomia: increased maternal weight gain during gestation, increased number of births until infant No. 3, white race, increased maternal age, poor glycemic control from the 20th week of gestation, and increased insulin dose. Advance White classification and increased duration of diabetes were predicted to be inversely related. In addition, macrosomia was hypothesized to predispose to selected adverse perinatal outcomes including premature labor, birth asphyxia, birth injury, hypoglycemia, polycythemia, and respiratory distress syndrome. From 1978 to 1986, 127 pregnancies were prospectively studied, 86 of the total number of women were entered prior to 10 weeks' gestation, and 41 were entered after 10 weeks' gestation. Patients monitored blood glucose at least twice daily with glycemic control achieved by "split-dosage" regimens of insulin. Glycohemoglobin was measured monthly. Pregnancy dating was based on the date of the last menstrual period and the Ballard score of the infant at birth. Macrosomia was defined as a birth weight greater than the 90th percentile of the intrauterine growth curves of Lubchenco. Of the babies born to mothers with insulin-dependent diabetes, 43% were large for gestational age and 57% were appropriate for gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary eosinophilic granuloma complicating pregnancy.

The first known case of pregnancy complicated by pulmonary eosinophilic granuloma is reported. The patient developed dyspnea late in pregnancy, but there was no objective evidence of deterioration in arterial blood gases or pulmonary function tests. Cesarean section was required at 36 weeks' gestation because of falling estriol levels in the presence of a breech presentation and an inability to induce cervical dilation. Maternal, postoperative, and neonatal courses were normal. Recommendations are made concerning the treatment of similar patients with similar symptoms.

Neonatal outcome among low birth weight infants delivered spontaneously or by low forceps.

In a population of 1065 singleton, low birth weight infants (1000 to 2500 g) delivered vaginally from vertex presentation, the neonatal mortality and morbidity of 394 delivered by low forceps were compared with those of 671 delivered spontaneously. There were no significant differences between the groups, either across the population as a whole or among any of the following birth weight subgroups: 1000 to 1500 g, 1501 to 2000 g, and 2001 to 2500 g. The data in the current study, as well as those from previous reports, argue against the routine use of prophylactic low forceps delivery and in favor of a more individualized approach to the vaginal delivery of infants in vertex presentation in this weight group.

Relationship of nonstress test reactivity and gestational age.

The relationship between gestational age and reactivity during the nonstress test was evaluated in 297 high-risk patients. When the incidence of nonreactive tests at gestational ages of 28 to 44 weeks was evaluated week-by-week, either on the basis of tests performed or patients tested, there was no statistically significant relationship between reactivity and gestational age (P = .184 tests; P = .222 patients). Four grouped gestational-age intervals were evaluated. Interval A consisted of the period from 28 to 32 weeks' gestation, interval B consisted of the period from 33 to 36 weeks' gestation, interval C consisted of the period from 37 to 41 weeks' gestation, and interval D consisted of the period from 42 to 44 weeks' gestation. The incidences of nonreactive tests were 15.3, 3.9, 2.5, and 5.9% in intervals A, B, C, and D, respectively. The differences in the incidences of nonreactive tests between those performed in intervals A and B and intervals A and C were highly statistically significant (P less than .001). Differences in the incidences between other intervals did not reach statistical significance. The incidences of patients who experienced a nonreactive test were 10.2, 2.4, 2.8, and 4.7% in intervals A, B, C, and D, respectively. The differences in the incidences of patients who experienced a nonreactive test in intervals A and B and intervals A and C were highly statistically significant (P less than .001). Differences in the incidences between other intervals did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of angiotensin II and brain natriuretic peptide in the placentas of normal and diabetic women.

OBJECTIVE: To evaluate the effects of angiotensin II and brain natriuretic peptide on the placental vasculature of diabetic women. METHODS: Term placentas from five diabetic women and five nondiabetic controls were collected. Isolated placental cotyledons were perfused dually with fetal perfusion pressure as an index of vascular response. The effect of angiotensin II (10(-10)-10(-5) mol/L bolus injection) was established in the fetal-placental vasculature of all placentas in the absence or presence of brain natriuretic peptide (10(-8) mol/L final concentration). Data were analyzed using repeated measures analysis of variance and paired t test where appropriate. RESULTS: A significant vasoconstrictor response to angiotensin II was achieved in placentas of both diabetic and nondiabetic women (P < .001); however, the angiotensin II-induced increase in perfusion pressure was significantly greater in the diabetic group (P < .01). Significant attenuation of vasoconstrictor response to angiotensin occurred in the presence of brain natriuretic peptide in placentas of both nondiabetic (P < .0025) and diabetic (P < .025) women, but the effect was more prominent in the diabetic group. CONCLUSION: The in vitro placental vasculature of diabetic women is more sensitive to angiotensin II than is the in vitro placental vasculature of nondiabetic women. The attenuation exerted by brain natriuretic peptide on angiotensin II-induced vasoconstriction is more prominent in placentas from diabetic women compared to those from nondiabetic women.

Hypertension during pregnancy in insulin-dependent diabetic women.

Insulin-dependent diabetic patients are at increased risk for hypertensive disorders of pregnancy. This study was designed to study prospectively the rate of pregnancy-induced hypertension (PIH) in 175 insulin-dependent diabetic pregnancies (88 White classes B-C, 87 classes D-RT). Pregnancy-induced hypertension was defined as two or more occurrences after 20 weeks' gestation of a mean arterial pressure (MAP) of 105 mmHg or greater or an increase of 20 mmHg or greater from the baseline MAP. The rate of PIH in the diabetic population was 15.4% and was significantly associated with nulliparity, poor glycemic control in the first and second trimesters, and advanced White class. Neonatal outcome was not significantly altered in the presence of PIH. We speculate that improved glycemic control throughout pregnancy might reduce the rate of this complication in diabetic patients.

Decreased amniotic fluid magnesium concentration in diabetic pregnancy.

Amniotic fluid samples from 21 diabetic pregnant women were pair-matched for gestational age with 21 samples obtained from nondiabetic women, and analyzed for magnesium concentration. Mean +/- standard deviation amniotic fluid magnesium concentration (mg/dL) was 0.86 +/- 0.21 in the diabetic group and 1.06 +/- 0.22 in the control group (P less than .001). It is concluded that in the diabetic pregnancy, a state of fetal magnesium deficiency exists. This deficient state may contribute to neonatal hypocalcemia in infants of diabetic mothers.