Clinical management of a pregnant patient with type I osteogenesis imperfecta using quantitative ultrasonometry--a case report.

INTRODUCTION: We present a case report on the clinical management of a pregnant patient with type I osteogenesis imperfecta (OI). OI is an inherited disease with an incidence in pregnancy of 1 in 25 000 to 30 000. The basic pathology is a defective maturation of type I collagen. CASE PRESENTATION: A 35-year-old primigravida with OI and a prior history of 30 fractures is presented. During pregnancy, all antenatal ultrasound scans showed normal fetal development. At 21 weeks of gestation, the patient had to be immobilised for 3 weeks due to premature labour. At 32 weeks of gestation, the patient developed increasing pain of the lumbar spine and arthralgia of the hip joints leading to hospitalisation. After a new fracture could be excluded, treatment with metamizole and a daily dose of 1000 mg of calcium and 800 IU of vitamin D was initiated. Since her first visit at 13 weeks of gestation, the patient was monitored by Quantitative Ultrasonometry (QUS) of the phalanges to estimate the fracture risk. There was a clinically relevant continuous decrease in the amplitude-dependent speed of sound (AD-SOS) and the T-score from 2052 m/sec and - 1.03 at 12 weeks 6 days of gestation to 2004 m/sec and - 1.71 at 32 weeks 5 days of gestation which correlated with the increase in pain. At 33 weeks 5 days of gestation, an elective caesarean section was performed due to intolerable pain and increased fracture risk. CONCLUSION: During pregnancy, our patient with OI showed a continuous decline in QUS variables and T-scores as well as a clinically significant increase in lumbar pain and arthralgia of the hip joints finally leading to an elective caesarean section. During pregnancy, no maternal fracture occurred, and the neonate showed a normal skeletal status without clinical signs of OI.

Biochemical markers of bone turnover during pregnancy: a longitudinal study.

OBJECTIVE: The objective of this study was to prospectively investigate the effect of pregnancy on biochemical markers of bone turnover in healthy pregnant women. METHODS: During the course of our longitudinal study, biochemical markers of bone remodeling were measured in all three trimester of pregnancy (first trimester: 12.5+/-1.8 SD, second trimester: 21.6+/-1 SD, third trimester: 34.8+/-1.6 SD weeks of gestation). Serum type I collagen C-telopeptides (CTX) and a crosslinked peptide of the carboxy-terminal telopeptide of type I collagen (ICTP) were used as markers of bone resorption. Bone alkaline phosphatase (BAP) and the N-terminal propeptides of type I collagen (PINP) were used as biochemical markers of bone formation. Blood samples for the analysis of all 4 biochemical markers according to each trimester of pregnancy were available in 49 patients. RESULTS: The main changes for all biochemical markers were seen between the second and the third trimester. According to the markers of bone resorption, both serum CTX and ICTP showed a significant increase from the first to the third and from the second to the third trimester (p<0.001; median percentage change: CTX=101.5% and ICTP=40%). Concerning markers of bone formation, PINP showed a significant decrease from the first to the second trimester (p=0.001) followed by a significant increase from the second to the third trimester (p<0.001, 63.8%) and an overall increase from the first to the third trimester (p<0.001). BAP also showed a significant increase from the second to the third trimester (p<0.001; 51.7%) and an overall increase from the first to the third trimester (p<0.001). CONCLUSION: Markers of bone resorption were significantly increased during pregnancy. In contrast to bone resorption, markers of bone formation showed an increase as well as a decrease during pregnancy indicating a state of high bone turnover. This might coincide with the change in bone mineral density that was observed in some, but not all, studies using "dual-energy x-ray absorptiometry" (DXA) as well as "quantitative ultrasonometry" (QUS).

[Evaluation of quantitative ultrasonometry of bone in singleton and multiple pregnancies]. / Evaluierung der quantitativen Ultrasonometrie des Knochens bei Einlings- und Mehrlingsschwangerschaften.

OBJECTIVE: During pregnancy about 30 grams of calcium are transferred to a full-term neonate. The enormous demand for calcium can be regulated by compensatory mechanisms in the maternal metabolism such as elevated steroid hormone levels, increased intestinal absorption of dietary calcium, and renal conservation, but also by mobilization of calcium from the maternal skeleton. Therefore we have investigated whether a decrease in maternal bone mineral density (BMD) can be observed during pregnancy and whether it differs between singleton and twin pregnancies. METHODS: Quantitative ultrasonometry (QUS) was performed at the distal metaphysis of the phalanges (digits II - V). 54 singleton pregnancies and 6 twin pregnancies were longitudinally followed throughout pregnancy. In each trimester the amplitude-dependent speed of sound (AD-SOS) and the bone transmission time (BTT) were measured. RESULTS: In 54 singleton pregnancies significant decreases in AD-SOS of 1.9 % (p

Fetal lung development in pregnancies of diabetic women assessed by quantitative ultrasonic tissue characterization.

OBJECTIVES: This study was performed to compare quantitative ultrasonic tissue characterization of the fetal lung at different gestational ages in uncontrolled diabetic patients with that in normal uncomplicated pregnancies. METHODS: A total of 44 women at 24-37 weeks' gestation with the diagnosis of diabetes in pregnancy were enrolled. Data were compared to those of the control group, which consisted of 140 women with uncomplicated pregnancies of the same gestational age. Longitudinal and transverse sections of the fetal thorax and upper abdomen were examined. A region of interest of constant size was defined and the tissue-specific gray scale was determined by using interactive software. RESULTS: Compared with normal pregnancies, fetal lungs of diabetic pregnancies have a higher echogenicity between 28 and 37 weeks of gestation. The lung mean gray values (MGV) only differed significantly between 30 and 31 weeks of gestation in the group with diabetes (P = 0.033) compared to the control group. The MGV of the liver in diabetic and normal pregnancies is similar during pregnancy, significant differences being found only at 30-31 weeks of gestation (P = 0.038). The lung-to-liver ratio in the control group showed a significant increase from 24 to 31 weeks and a slight non-significant decrease after 31 weeks. The ratio in the group with diabetes increased slightly up to week 33 and decreased slightly afterwards. CONCLUSION: Fetal lung MGV in uncontrolled diabetic pregnancies compared to that in uncomplicated pregnancies differs significantly only between 30 and 31 weeks of gestation.

[Combination therapy for fetal supraventricular tachycardia with flecainide and digoxin]. / Kombinationstherapie einer fetalen supraventrikulären Tachykardie mit Flecainid und Digoxin.

Persistent fetal supraventricular tachycardia (SVT) with more than 210 bpm frequently leads to congestive heart failure. We report on a case with SVT and congestive heart failure that converted into sinus rhythm within 19 days of therapy with flecainide and beta-acetyldigoxin. A 32-year-old II gravida I para (25 + 1 weeks of gestation) presented with fetal SVT of 267 bpm. A non-immunologic hydrops fetalis was diagnosed by ultrasound showing ascites, pleural and pericardial effusion and tricuspid regurgitation. Within 19 days of combination therapy with flecainide and digoxin, cardioversion was achieved. After 36 days of therapy no more signs of cardiac failure could be detected. A healthy boy was born at 38 + 6 weeks of gestation. Although cardioversion is expected after 72 h of therapy according to the literature, this fetus converted into sinus rhythm on day 19 of therapy. This indicates that patients should not be considered resistant to treatment within the first 3 - 4 days.

Polymorphisms within glutathione S-transferase genes and initial response to glucocorticoids in childhood acute lymphoblastic leukaemia.

In children with acute lymphoblastic leukaemia (ALL) treated according to protocols of the Berlin-Frankfurt-Münster (BFM) study group, the initial response to prednisone is the strongest predictor of therapy outcome. Glutathione S-transferases (GSTs) have been implicated in glucocorticoid resistance. In order to assess a potential association of phenotypically relevant GST polymorphisms with prednisone response in childhood ALL, we conducted a case-control study of 45 prednisone poor-responders (cases) and 90 prednisone good-responders (controls) who were frequency matched according to initial white blood cell count. In addition, we analysed the association of GST genotypes with relapse of leukaemia. In univariate analysis, homozygous deletion of GSTT1 (null genotype) conferred a 6.7-fold reduction in risk of prednisone poor-response compared to individuals who were either heterozygous or homozygous for GSTT1 [odds ratio (OR) = 0.15, P = 0.071; multivariate odds ratio = 0.18, P = 0.117]. GSTM1 and GSTP1 genotypes did not show any association with prednisone response. In addition, risk of relapse was predicted strongest by the GSTT1 genotype. In univariate analysis, the GSTT1 null genotype conferred a 5.9-fold reduction in risk of relapse compared to the heterozygous or homozygous presence of GSTT1 (OR = 0.17, P = 0.095; multivariate OR = 0.23; P = 0.173). No associations of the GSTM1 genotype with risk of relapse were observed. GSTP1 codon 105 and codon 114 polymorphisms were predominantely associated with central nervous system relapse. Our results add further support to the hypothesis that genetic polymorphisms within specific GST genes might be of clinical importance in childhood ALL.