Association between maternal and child leptin levels 9 years after pregnancy complicated by gestational diabetes.

Obesity is a state of relative leptin resistance, and obesity in childhood is associated with an increased incidence of type 2 diabetes in later life. Offspring of mothers with gestational diabetes mellitus (GDM) are at increased risk of obesity. A cohort consisting of 64 mothers, 33 GDM and 31 controls screened for diabetes during the index pregnancy together with their 9-year-old offspring were studied. Our hypotheses were: 1) an elevated child leptin is associated with elevated maternal leptin in GDM mothers 9 years post delivery; and 2) child leptin at 9 years serves as a marker for incipient insulin resistance. By univariate analyses, child leptins were only significantly correlated with maternal leptins among the offspring of GDMs (OGDM) (r = 0.59; p = 0.001). By multivariate analyses, child leptin for the total study group was significantly associated with child body mass index (BMI) (R(2) = 0.65; p < 0.0001), child fasting insulin (R(2) = 0.08; p = 0.03), and female gender (R(2) = 0.28; p = 0.001). In addition, among OGDM child leptin was associated with maternal leptin (R(2) = 0.14; p = 0.005). Our results suggest that there is an association between maternal and child leptin levels 9 years after a pregnancy complicated by gestational diabetes.

Association of interpregnancy interval with uterine scar failure in labor: a case-control study.

OBJECTIVE: The aim of this study was to determine whether a short interpregnancy interval is associated with uterine scar failure in laboring patients with previous low transverse cesarean delivery. STUDY DESIGN: This was a case-control study of uterine scar failures among laboring patients with previous low transverse cesarean delivery. Control patients underwent abdominal delivery during labor after failure of an attempted vaginal birth after cesarean delivery in the same month as case patients. RESULTS: An interpregnancy interval of <6 months was significantly more prevalent among case patients with uterine scar failure (P =.02). Mean interpregnancy interval was less in all cases of uterine scar failure (P = .06). CONCLUSIONS: Interpregnancy interval was inversely associated with likelihood of uterine scar failure during subsequent labor.

Outcome of very low birth weight infants with histopathologic chorioamnionitis.

OBJECTIVE: To determine neonatal outcome at 7 months of corrected age in very low birth weight (VLBW) infants with placental chorioamnionitis. METHODS: We conducted a cohort study of 287 VLBW infants delivered as a result of preterm premature rupture of membranes (PROM) or preterm labor. Control subjects (n = 123) had placentas with absent umbilical cord inflammation and absent or low-grade membrane inflammation. Case subjects (n = 164) had moderate membrane inflammation or any umbilical cord inflammation. Neonatal and 7-month outcomes were compared. A power analysis showed that 98 total subjects were needed to reject the two-sided null hypothesis with a difference in mean Bayley index scores of at least 8. RESULTS: Infants in the study group had significantly more preterm PROM, antenatal antibiotics, lower birth weight, lower gestational age, longer duration of ruptured membranes, and clinical chorioamnionitis. Intraventricular hemorrhage occurred more commonly in infants with placentas demonstrating chorioamnionitis (relative risk = 1.6, 95% confidence interval 1.1, 2.4, P =.013). One hundred sixty-seven (69%) of the 243 surviving infants had 7-month follow-up. There was no difference between cases and controls in mean Bayley mental developmental index (93 compared with 90, P =.25), psychomotor developmental index (89 compared with 90, P =.68), or in the number of infants that were developmentally delayed. CONCLUSION: Despite a higher frequency of intraventricular hemorrhage, no difference in developmental scores was detected at 7 months of corrected age in VLBW infants with histologic chorioamnionitis.

Corticosteroid dynamics in the nonpregnant, pregnant, and postpartum spontaneously hypertensive rat.

Factors responsible for hypertension in the spontaneously hypertensive rat (SHR) remain under investigation. As in human pregnancy complicated by essential chronic hypertension, the hypertension of the pregnant SHR subsides and returns postpartum. Because corticosteroid excess can cause hypertension, we examined several aspects of adrenocortical activity as potentially affecting the reported blood pressure profiles of nonpregnant, term pregnant, and postpartum SHR, using normotensive Wistar-Kyoto (WKY) rats as controls. We found that corticosterone levels were comparable in nonpregnant SHR and WKY rats, and unaffected by pregnancy. No differences were detected postpartum. Although pregnancy was accompanied by significant increases in plasma aldosterone levels, no interbreed differences were observed, which remained the case postpartum. Single adrenal cell secretion of aldosterone and corticosterone, as detected by reverse hemolytic plaque assay, yielded similar results in the pregnant and postpartum rat. Hormone responses to dietary manipulations in the nonpregnant and pregnant SHR and WKY suggest an important role for ACTH, and a lesser one for AII in the regulation of corticosteroids. In situ hybridization histochemistry, using a probe that detects both P450c11beta and P450c11AS mRNA, revealed comparable message density and zonal distribution in adrenals from pregnant and nonpregnant SHR and WKY rats. Breed- and pregnancy-dependent differences in adrenal expression of P450scc, P450c11beta, and P450c11AS were noted. In summary, our findings suggest that although some discrepancies exist in the aspects of adrenocortical activity examined, they are unlikely to be etiologic in the blood pressure profile observed in nonpregnant, pregnant, and postpartum SHR.

Adrenocortical activity in fetal SHR and WKY rats.

There is increasing evidence that the intrauterine milieu and corticosteroid exposure play a role in the etiology of hypertension. We examined adrenocortical gene expression and circulating corticosteroids in the d 21 fetal spontaneously hypertensive rat (SHR) and its normotensive genetic control, the Wistar-Kyoto (WKY) rat. By RNase protection assays, we found no differences in the relative abundances of mRNAs for P450scc and P450c11beta, and barely detectable P450c11AS mRNA in the adrenals of fetal SHR and WKY rats. P450c11B3 RNA was undetectable by reverse transcription polymerase chain reaction in both SHR and WKY fetuses. The zonal expression of P450c11 mRNA was comparable in SHR and WKY fetuses by in situ hybridization histochemistry. There were no significant differences in peripheral levels of aldosterone and corticosterone by radioimmunoassay in fetal SHR and WKY rats. Based upon the absence of distinct differences in the aspects of adrenocortical activity examined, it is unlikely that they are integral in the programming of hypertension in this model.

Influence of chorioamnionitis on developmental outcome in very low birth weight infants.

OBJECTIVE: To determine the effect of exposure to chorioamnionitis on developmental outcome in very low birth weight (VLBW) infants. METHODS: Five hundred four maternal charts (97% of all VLBW infants delivered from 1990 to 1994) were reviewed. A historical cohort study of the 330 infants delivered secondary to preterm premature rupture of membranes or preterm labor was performed. Case subjects (71) were delivered of mothers with chorioamnionitis by clinical criteria; control subjects (259) were delivered of mothers without chorioamnionitis. Bayley index scores at 7 months' corrected age and special care nursery outcomes were compared. One hundred seventy-three subjects were necessary to reject the two-sided null hypothesis with 80% power with a difference in mean Bayley index scores of at least 8. RESULTS: Neonatal sepsis (8.5% compared with 1.9%; odds ratio [OR] = 4.7, 95% confidence interval [CI] 1.4, 15.9, P = .015) and a low 5-minute Apgar (72% compared with 55%; OR = 2.1, CI 1.2, 3.8, P = .012) occurred more frequently in the chorioamnionitis group. One hundred eighty-seven (68%) of 273 surviving neonates had follow-up. Cases and controls were similar in mean Bayley mental developmental index (91.2 compared with 91.8, P = .84), Bayley psychomotor developmental index (89.8 compared with 89.1, P = .82), and number of infants developmentally delayed. Duration of exposure to chorioamnionitis did not affect neonatal outcome. CONCLUSION: Despite higher rates of sepsis and low Apgar scores, no difference in outcome at 7 months of corrected age was detected in VLBW infants exposed to chorioamnionitis. Contemporary neonatal management may reduce the adverse effects of this exposure.

Adrenocortical imprint in the fetus of a diabetic gestation.

Offspring of diabetics are at increased risk for diabetes as adults. As corticosteroids are intimately involved in glucose homeostasis, we investigated aspects of corticosteroid activity in the late gestation fetuses of control, moderately diabetic and insulin-controlled streptozotocin-induced diabetic rats. We found that moderate maternal diabetes had no effect upon litter size or fetal body weight. Uncontrolled maternal diabetes was accompanied by fetal hyperglycemia, hyperinsulinemia and elevated aldosterone. Maternal insulin treatment normalized fetal glucose and aldosterone; fetal insulin and corticosterone levels increased. Maternal diabetes had no effect upon fetal adrenal expression of P450scc mRNA; the abundance of P450c11beta mRNA increased, and returned to that of the control gestation upon insulin treatment. P450c11AS mRNA was barely detectable, and decreased in the fetuses of insulin-treated diabetics. P450c11B3 mRNA was undetectable in all fetal groups. Our results implicate aspects of maternal diabetes in the expression of a fetal adrenocortical imprint, manifested as a greater abundance of P450c11beta mRNA. Although not accompanied by elevated corticosterone in the fetus, this imprint could ultimately allow for greater potential corticosterone production in response to typical stimuli, and thus contribute to the tendency towards glucose dysregulation in these offspring of diabetic gestations.

Adrenocortical activity in the newborn spontaneously hypertensive rat.

Blood pressure is reportedly elevated in the spontaneously hypertensive rat (SHR) neonate, the etiology of which remains unclear. Aberrations in the hypothalamic-pituitary-adrenal axis have been implicated, as it is well accepted that excess corticosteroids are associated with hypertension. We examined aspects of adrenocortical activity in the neonatal SHR 1 to 21 days old and its normotensive genetic control, the Wistar-Kyoto rat (WKY). We found a fourfold greater abundance of P450scc mRNA in adrenals of SHR versus WKY day 1 neonates, and increasing but comparable abundance of adrenal P450c11B mRNA on neonatal days 1 to 21. The pattern of P450c11AS mRNA expression was distinctly different in the adrenals of SHR and WKY neonates; the relative abundance of this mRNA in SHR increased 15-fold over the 21-day period examined, whereas that in WKY remained fairly stable. RT-PCR for the presence/abundance of adrenal P450c11B3 mRNA showed absence in day 1 SHR and WKY, comparable abundances on neonatal days 7 and 14, and a distinctly greater abundance in the day 21 SHR adrenals. Peripheral corticosterone levels were threefold greater in the day 1 SHR neonate; aldosterone levels were elevated in both the SHR and WKY day 1 neonate. Thereafter, corticosterone and aldosterone levels were comparable on days 7, 14, and 21, although the anticipated depression in circulating corticosterone levels typical of the stress hyporesponsive period was noted in both SHR and WKY neonates. Although patterns of adrenocortical activity differ in the newborn SHR and WKY rat, our findings do not support an etiologic role for corticosteroids in the reported hypertension of the SHR. However, observed differences in corticosteroid profiles may augment or have a permissive effect upon the etiologic factor(s).

Prenatal ultrasound diagnosis of abdominal aortic aneurysm with fibrotic occlusion in aortic branch vessels.

In a 35-year-old multiparous patient, an ultrasound scan performed at 32 weeks' gestational age for size less than dates revealed an appropriately grown fetus with a two-vessel umbilical cord. Also noted were dilated, tortuous abdominal and pelvic vessels. A scan at 33.5 weeks confirmed the two-vessel cord and noted a widely dilated abdominal aorta and a left foot 2 cm shorter than the right. Delivery at 36 weeks was followed by a neonatal course complicated by thromboses, renovascular hypertension, and a newly patent ductus with pulmonary hypertension. Successful ligation was followed by acute pulmonary hypertension, cardiac dysfunction and death. Autopsy findings included aneurysmal dilation of the abdominal aorta without evidence of arterial wall pathology.

Chronic relapsing thrombotic thrombocytopenic purpura in pregnancy: a case report.

Thrombotic thrombocytopenic purpura (TTP) is a disorder of unknown etiology affecting the microcirculation of multiple organ systems. Plasma therapy has significantly reduced the mortality rate; thus, an increased incidence of recurrence has been noted. Since corticosteroids, antiplatelet agents, and splenectomy do not prevent recurrences, monthly plasma infusion have been instituted to decrease the risk of recurrence. However, in pregnancy, increase in frequency of plasma infusions to weekly or biweekly intervals has been associated with avoidance of placental infarcts. This is the first report of a successful pregnancy in which bimonthly prophylactic single plasma-exchange plasmapheresis was the treatment regimen with no obvious maternal-fetal morbidity.

Adrenal pseudocyst in pregnancy. A case report.

BACKGROUND: Adrenal cysts are rare tumors that have a female: male predominance of 2-3:1. They are, however, rarely encountered during pregnancy but should be considered in the differential diagnosis of flank pain. CASE: A 33-year-old woman, gravida 5, para 3013, was transferred to a tertiary care center at 14 weeks' gestation with unrelenting flank pain and gastrointestinal symptoms. Ultrasound and magnetic resonance imaging identified a large mass. After failed conservation therapy, laparotomy revealed an adrenal cyst, which was excised. The pregnancy proceeded uneventfully and ended in a term delivery. CONCLUSION: This is the second documented case of pregnancy associated with an adrenal cyst. Surgical excision remains the definitive therapy. Pregnancy appears unaffected by such a cyst.

Utilization of routine ophthalmologic examinations in pregnant diabetic patients.

OBJECTIVE: To determine the appropriate frequency of ophthalmologic examinations for retinopathy during gestation in diabetics categorized according to White's classification. STUDY DESIGN: Retrospective review was performed over the period of 1989-1994. Inclusion criterion for gestational diabetics was a late second or early third trimester ophthalmologic examination. Inclusion criteria for classes B-R were a first trimester and third trimester or early postpartum examinations. RESULTS: Of 300 charts reviewed, 100 met inclusion criteria. None of the gestational diabetics had retinopathy. Of class B patients (n = 21), 19% had retinopathy, with 11% progression in background retinopathy; none developed severe background or proliferative disease. In class C patients (n = 9), 56% had retinopathy, 33% with progression; none developed severe background or proliferative disease. Thirteen patients were class D; 92% had background retinopathy, in whom 45% showed progression, 31% with severe background retinopathy; none developed proliferative disease. Combined classes F, R, RF represented 13 patients; 100% demonstrated retinopathy; 46% progressed, 77% with proliferative disease; 15% required laser treatment during the pregnancy. CONCLUSIONS: Routine ophthalmologic examinations in gestational (class A) diabetics have little utility. Results suggest that the need for subsequent ophthalmologic examinations can be based upon White's classification and initial examination results. Classes B and C do not require every trimester eye examinations. Rigorous follow-up is warranted in classes D-R.

Endocrine disorders in pregnancy.

Disorders of the pituitary gland such as diabetes insipidus, pituitary adenomas, and hyperprolactinemia, disorders of the thyroid gland such as Graves' disease and hypothyroidism, and diseases of the adrenal gland such as adrenocortical insufficiency and Cushing's syndrome can complicate pregnancy. The goals of this article were to provide a basic scientific understanding of the normal function of these endocrine glands, their pregnancy-related changes, and suggestions for diagnosis and treatment of maternal and fetal endocrine disorders during pregnancy. Antenatal recognition and appropriate management of the disorders that especially affect the fetus (i.e., maternal Graves' disease, fetal hypothyroidism, and congenital adrenal hyperplasia) is essential in order to prevent fetal and neonatal morbidity and mortality.

Expectant and active management of preterm premature rupture of membranes.

Optimal management of PPROM remains controversial. Expectant management is a viable alternative only if there is no evidence of infection, advanced labor, or fetal distress. In these cases, aggressive intervention is appropriate, regardless of gestational age. The goal of expectant management is the achievement of increased gestational age at the time of delivery, given the tremendous potential advantage to be gained during the period between 26 and 34 weeks' gestation, an interval during which perinatal mortality decreases sharply. The potential value of corticosteroids and prophylactic antibiotics is discussed elsewhere in this issue. The power limitations of the previous studies, which considered amniocentesis and tocolytic therapy, preclude firm conclusions and enthusiastic recommendation for their routine inclusion in the expectant management of PPROM.

Increases in plasma atrial natriuretic peptide concentration antedate clinical evidence of preeclampsia.

Atrial natriuretic peptide (ANP) concentrations are typically elevated in hypervolemic states. However, ANP levels have been reported to be increased in the peripartum period in women with preeclampsia, a disorder characterized by central hypovolemia. We postulated that ANP levels are elevated in preeclamptic patients before clinically evident disease. ANP concentrations were determined in three groups: uncomplicated pregnancies, pregnancies complicated by preeclampsia, and non-pregnant reproductive-aged women. The former groups were matched for gestational age at plasma sampling and delivery. The plasma samples, obtained prospectively from each patient during the first, second, and third trimesters and within 72 h postpartum, were frozen before RIA. A significant gestational increase in ANP was noted in both groups of pregnant women, with third trimester levels exceeding first trimester levels (P less than 0.05). Consistent with previous reports, ANP levels were elevated in overtly preeclamptic patients vs. matched controls in the third trimester. The ANP concentration was also significantly increased during the second trimester in women destined to develop preeclampsia. Postpartum ANP values decreased in the preeclamptic group to approach the level in normal patients postpartum. Thus, it appears that the stimuli of ANP secretion differ in uncomplicated and preeclamptic patients. Moreover, an elevation of plasma ANP is detectable before the onset of clinical evidence of preeclampsia.

Zone-specific regulation of two messenger RNAs for P450c11 in the adrenals of pregnant and nonpregnant rats.

Adrenal mitochondria possess two steroidogenic cytochrome P450s. P450c11 converts deoxycorticosterone to corticosterone and aldosterone, and P450scc converts cholesterol to pregnenolone. These P450s receive electrons from NADPH via adrenodoxin reductase and adrenodoxin. A single bovine P450c11 protein has 11-hydroxylase, 18-hydroxylase, and 18-oxidase activities, but this series of enzymatic steps may be mediated by more than one enzyme in rats. Enzymatic assays of purified rat mitochondrial proteins have suggested that one enzyme found in all zones of the adrenal cortex has both 11- and 18-hydroxylase activities, whereas another enzyme, found exclusively in the zona glomerulosa, catalyzes 18-hydroxylation and 18-oxidation of corticosterone. We studied the number and zonal distribution of P450c11 mRNA species in the rat adrenal and how these mRNAs are regulated in the adrenals of normal and pregnant rats. Rats synthesize two similar, but distinct, P450c11 mRNAs. One, P450c11A, is found in both the zona glomerulosa and fasciculata/reticularis, whereas the second, P450c11B, is found only in the zona glomerulosa. The abundance of neither P450c11A mRNA nor P450c11B mRNA is affected by a high-salt diet. However, when rats receive a low-salt diet, P450c11A mRNA decreases and P450c11B mRNA increases. Dexamethasone decreases the amount of P450c11A mRNA without affecting P450c11B mRNA. The combination of a high-salt diet and dexamethasone decreases the amount of both mRNAs further to almost undetectable amounts. Rats given a low-salt diet and dexamethasone have a dramatic increase in the abundance of P450c11B mRNA. Thus both forms of P450c11 mRNA are regulated independently in the rat adrenal cortex. In situ hybridization studies show that only the P450c11 found in the zona glomerulosa is regulated by salt treatment in vivo, whereas glucocorticoid treatment in vivo regulates P450c11 in all zones. In the adrenals of pregnant rats, P450c11B is regulated in a similar fashion to its regulation in the nonpregnant rat adrenal, despite major differences in sodium retention and intravascular volume in pregnant and nonpregnant rats. In the pregnant rat, a low-salt diet increases the abundance of P450c11B to a greater degree than in the nonpregnant rat. By contrast, dexamethasone does not diminish the abundance of P450c11A mRNA in the pregnant rat but reduces it to an almost undetectable amount in the nonpregnant rat. Thus, the regulation of glucocorticoid and mineralocorticoid production in the pregnant and nonpregnant rat occurs by different mechanisms.

Multiple myeloma in pregnancy: a case report.

Multiple myeloma, a generalized malignancy resulting from the proliferation of a single clone of neoplastic plasma cells, occurs rarely in pregnancy. This is the fifth documented case of pregnancy in a woman with this disorder. Clinical features of multiple myeloma include bone pain, pathologic fractures, neurologic deficits, and frequent bacterial infections. Laboratory evaluation often reveals hypercalcemia, anemia, and some degree of renal failure. Both radiation therapy and chemotherapy are used to treat multiple myeloma. Although the ultimate prognosis of a woman with this disease is poor, the offspring are apparently unaffected.

Comparative in vitro responses of fetal, pregnant and non-pregnant rabbits' adrenal glands to steroidogenic agents.

The in vitro secretion of aldosterone and corticosterone by the adrenal glands of fetal (day 30), pregnant and non-pregnant rabbits was examined under basal and stimulated conditions. In general, non-pregnant animals basally secreted less aldosterone than either pregnant or fetal rabbits, whereas basal corticosterone secretion by pregnant animals exceeded that of either fetal or non-pregnant animals. At similar doses of adrenocorticotropin (ACTH), fetal and pregnant adrenal glands produced comparatively more aldosterone than non-pregnant animals, while corticosterone secretion was accelerated to a greater degree in fetal rabbits than in the other groups. Angiotensin II had its greatest effect on the aldosterone secretory rates of fetal and non-pregnant animals without affecting corticosterone secretion in any group. Elevated potassium (K+) enhanced the secretory rates of aldosterone and corticosterone in fetal animals, while increasing only aldosterone secretion in non-pregnant rabbits. Serotonin accelerated aldosterone secretion in all animals, whereas it increased corticosterone secretion only in non-pregnant animals. These results suggest that (1) in fetal rabbits, the secretory rates of both aldosterone and corticosterone are regulated primarily by ACTH and to a much lesser extent by angiotensin II and K+, (2) the corticosterone secretory rates of pregnant and non-pregnant rabbits are controlled mainly by ACTH, and (3) aldosterone secretion by non-pregnant animals is regulated primarily by angiotensin II and secondarily by ACTH and K+, while in pregnant animals ACTH may be the primary regulator of aldosterone secretion as it is in the fetus.