Management of Severe Graves' Hyperthyroidism in Pregnancy Following Immune Reconstitution Therapy in Multiple Sclerosis.

CONTEXT: Alemtuzumab (ALZ), a CD52 monoclonal antibody, is highly efficacious in multiple sclerosis; however, side effects are common. Autoimmune thyroid disease (Graves' disease and Hashimoto thyroiditis) is a well-known complication of ALZ. Treatment of ALZ-induced Graves' disease can be challenging, and even more difficult during pregnancy. CASE DESCRIPTION: We present a case of severe ALZ-induced Graves' disease with a rapid increase in thyrotropin receptor antibodies (TRAb 240 IU/L) and thyrotoxicosis in early pregnancy. Treatment with high doses of antithyroid medication was needed. There was high risk of both fetal and neonatal thyrotoxicosis. Serial fetal sonography showed normal development. The newborn baby presented high levels of TRAb (240 IU/L) and developed neonatal thyrotoxicosis on day 8. Adequate monitoring, treatment, and follow-up of the newborn baby ensured normal thyroid function until disappearance of TRAb 6 weeks after birth. CONCLUSION: Multiple sclerosis patients treated with ALZ may develop severe Graves' disease with an increased risk of both fetal and neonatal thyrotoxicosis. Close follow-up with a multidisciplinary approach is needed to ensure a healthy outcome.

Determination of fetal RHD type in plasma of RhD negative pregnant women.

Alloimmunization against the RhD antigen is the most common cause of hemolytic disease of the fetus and newborn. Antenatal anti-D prophylaxis in addition to postnatal anti-D prophylaxis reduces the number of RhD-immunizations compared to only postnatal administration. Cell-free fetal DNA released from the apoptotic trophoblastic placental cells into the maternal circulation can be used to determine the fetal RHD type in a blood sample from an RhD negative mother. Based on this typing, antenatal anti-D prophylaxis can be recommended only to RhD negative women carrying an RhD positive fetus, since only these women are at risk of developing anti-D. The objective was to establish and validate a method for non-invasive fetal RHD typing. The fetal RHD genotype was studied in 373 samples from RhD negative pregnant women (median gestational week 24). DNA extracted from plasma was analyzed for the presence/absence of RHD exon 7 and 10 in a real-time PCR. The RHD genotype of the fetus was compared with the serological RhD type of the newborn. In 234 samples, the fetal RHD test was positive and in 127 samples negative. There was one false positive and no false negative results. In 12 samples, the fetal RHD type could not be determined, in all of them due to a maternal RHD gene. This method gives a reliable detection of fetal RHD positivity in plasma from RhD negative pregnant women. Antenatal anti-D prophylaxis based on the predicted fetal RhD type will avoid unnecessary treatment of pregnant women carrying an RhD negative fetus.

Follow-up of TVT operations in 1,113 women with mixed urinary incontinence at 7 and 38 months.

A follow-up was done 7 and 38 months after tension-free vaginal tape (TVT) operation in 1,113 women with mixed urinary incontinence. Mixed incontinence and predominant bother were subjectively defined. The results were analyzed according to the women's predominant bother: stress incontinence, urge incontinence, or stress and urge incontinence equally. Across the groups, stress incontinence was cured in 87 and 83% of the women at 7 and 38 months, respectively, with no difference between the three groups. Women with predominant stress incontinence had significantly better results at both 7 and 38 months than those in the other groups, especially those predominantly bothered by urge incontinence. Women with mixed incontinence were significantly more often cured both objectively and subjectively at 7 than 38 months. Only 11% of the women experienced an increase in urge incontinence 38 months after TVT. Before a TVT operation, women with mixed urinary incontinence should be informed that their prognosis depends on their predominant bother. TVT is an appropriate treatment in mixed urinary incontinence, but women with predominant urge incontinence have poorer results than those with predominant stress incontinence.

A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia.

The study's objective was to identify HPA 1a-negative women and to offer them an intervention program aimed to reduce morbidity and mortality of neonatal alloimmune thrombocytopenia (NAIT). HPA 1 typing was performed in 100 448 pregnant women. The HPA 1a-negative women were screened for anti-HPA 1a. In immunized women, delivery was performed by Cesarean section 2 to 4 weeks prior to term, with platelets from HPA 1a-negative donors reserved for immediate transfusion if petechiae were present and/or if platelet count was less than 35 x 10(9)/L. Of the women screened, 2.1% were HPA 1a negative, and anti-HPA 1a was detected in 10.6% of these. One hundred seventy pregnancies were managed according to the intervention program, resulting in 161 HPA 1a-positive children. Of these, 55 had severe thrombocytopenia (< 50 x 10(9)/L), including 2 with intracranial hemorrhage (ICH). One woman with a twin pregnancy missed the follow-up and had one stillborn and one severely thrombocytopenic live child. In 15 previous prospective studies (136 814 women) there were 51 cases of severe NAIT (3 intrauterine deaths and 7 with ICH). Acknowledging the limitation of comparing with historic controls, implementation of our screening and intervention program seemed to reduce the number of cases of severe NAIT-related complications from 10 of 51 to 3 of 57.

The tension free vaginal tape operation for women with mixed incontinence: Do preoperative variables predict the outcome?

AIMS: The aims of our study were (1) to investigate subjective and objective outcomes after tension free vaginal tape (TVT) operations in mixed incontinent women, (2) to detect if preoperative subjective and objective variables predict the outcome, and (3) to evaluate whether the surgical outcome is different for women who preoperatively find stress incontinence, urge incontinence, or urge and stress incontinence equally the predominant bother. METHODS: A prospective cohort study was performed on 450 mixed incontinent women. A short-form disease-specific validated questionnaire, 24-hr pad test, standardized stress test, residual urine, and maximum urinary flow were used before and after a TVT operation. "Cure" was defined as a condition where the women were very satisfied with the TVT operation and had negative stress- and 24 hr pad tests. RESULTS: Preoperatively 69% had stress incontinence, 7% urge incontinence, and 24% urge and stress incontinence equally as the predominant bother. Cure rates were 80%, 52%, and 60%, respectively, in these groups. Postoperatively 43% of the women had no urge incontinence, while 49% were less, and only 8% were more bothered by urge incontinence. A higher preoperative urge incontinence index was correlated with significantly higher postoperative bother for all indices and leakage during 24-hr pad test. CONCLUSIONS: Mixed incontinent women with predominant stress incontinence had a better cure rate than those with predominant urge incontinence and those who were equally bothered by urge and stress incontinence. This point needs to be addressed when informing mixed incontinent women before a TVT operation.

[Women and epilepsy]. / Kvinner og epilepsi.

Women with epilepsy have several gender-specific problems, first of all related to pregnancy and childbirth. They do, however, also meet with several other, less well-recognised specific problems. Many women have a marked change in seizure frequency in relation to their menstrual cycle, and menstrual disorders and polycystic ovaries induced by the use of antiepileptic drugs (AEDs), or by the condition itself, are more frequent in women with epilepsy. Cosmetic side effects of AEDs including weight gain, hair loss and skin problems can significantly reduce compliance in drug treatment and thus affect seizure frequency. Enzyme-inducing AEDs reduce the effectiveness of oral contraceptives and may lead to unplanned pregnancies. A higher incidence of sexual problems in women with epilepsy has also been reported. In menopause, the seizure frequency may change in parallel with the endocrine changes and some AEDs may facilitate the development of osteoporosis. Better understanding and awareness of these problems among patients and health care professionals can relieve many of the gender-specific problems in women. The goal is to tailor the treatment to the needs of the individual woman.

[Pregnancy and birth in women with epilepsy]. / Svangerskap og fødsel hos kvinner med epilepsi.

More than 90 % of all women with epilepsy who take antiepileptic drugs (AEDs) will undergo normal pregnancies and give birth to children free of birth defects, though mothers on AEDs have two to three times higher incidence of malformations. Uncertainty exists regarding which AEDs are the most teratogenic. Valproate and carbamazepine have been associated with neural tube defects and phenytoin with cleft lip/palate and heart and urogenital defects. All women taking valproate and carbamazepine are advised to take 4 mg/day of folic acid at least one month before pregnancy and during the first trimester. Other women with epilepsy in fertile age are recommended to take 0.4 mg/day. Vitamin K 10 mg/day should be given the last 4 weeks to women on liver enzyme-inducing AEDs. During pregnancy, ultrasound should be performed around weeks 12 and 17. Amniocentesis for a-fetoprotein should be offered at week 15 to women using valproate and carbamazepine. Most women with epilepsy do not experience any change in seizure frequency during pregnancy and have normal vaginal deliveries. Use of monotherapy, lowest effective dose and retard formulations of AEDs, are advised during pregnancy. A seizure during labour is very rare, seen in 1-2 % of cases. Breast-feeding is encouraged for most AEDs, although barbiturates and benzodiazepines may have sedative effects on the infant. Pregnancy is generally safe in women with epilepsy, but preconception counselling and close collaboration during the pregnancy between the gynaecologist and the neurologist is warranted.

Umbilical artery Doppler flow velocity waveforms after transplacental amniocentesis.

OBJECTIVE: To assess the influence of transplacental versus nontransplacental needle passage during genetic amniocentesis on umbilical artery (UA) pulsatility index (PI) and fetal heart rate (FHR). METHODS: Genetic amniocentesis was performed in 205 women with no major fetal malformations detected by prenatal ultrasound at a median gestational age of 14 weeks and 3 days (range 13 weeks and 1 day to 18 weeks and 6 days). Chromosomal abnormalities were observed in five fetuses. These pregnancies were excluded from further analyses. The study group consisted of 56 of the remaining 200 women in whom amniocentesis had been performed transplacentally. As controls two patients with nontransplacental needle passage were chosen for each woman in the study group, matched for gestational age (+/- 3 days) and as far as possible for the indication for amniocentesis. The UA PI and the FHR were measured immediately before and after the amniocentesis. RESULTS: Amniocentesis did not cause significant changes in UA PI and FHR within or between the two groups. Division of the study population into three subgroups dependent on gestational age did not alter the results. Pregnancy outcome was similar in the two groups. CONCLUSION: Transplacental needle passage during amniocentesis did not induce any changes in UA PI or FHR relative to a group with nontransplacental amniocentesis.

Ultrasonographic monitoring of pregnancies complicated by red blood cell alloimmunization in a cohort with mild to moderate risk according to previous obstetric outcome.

AIM: To evaluate the detection rate of fetal anemia and pregnancy outcome as related to our policy of monitoring pregnancies with red blood cell alloimmunization. METHODS: From August 1997 to July 2000 35 pregnant women with maternal red blood cell alloantibodies were monitored by ultrasonographic measurements of the fetal spleen perimeter and peak systolic Doppler flow velocities of the middle cerebral artery, by semiquantification of maternal antibody titers and by general ultrasonographic and clinical evaluation. According to previous obstetric outcome they all had mild to moderate risk of developing fetal anemia. RESULTS: Eleven fetuses were anemic defined as a hemoglobin value < or = 2SD according to gestational age. A spleen perimeter > + 2SD and a middle cerebral artery peak systolic velocity > 95% prediction interval showed sensitivity and specificity of 64 and 92% and 45 and 100%, respectively. The area under receiver operating characteristic curves was 0.926 (95% CI 0.842-1.000; P < 0.001) for the spleen perimeter and 0.837 (95% CI 0.688-0.987; P < 0.01) for the middle cerebral artery peak systolic velocity. Cordocentesis was performed in one pregnancy only. None of the fetuses developed hydrops and all infants survived. Twelve women delivered before 37 weeks gestation. In 10 patients cesarean section was performed due to possible fetal anemia. Six of the 10 neonates had normal hemoglobin values. CONCLUSIONS: The ultrasonographic parameters did not predict all cases of fetal anemia defined as a hemoglobin concentration < or = 2SD according to gestational age. The present policy of monitoring seemed to reduce the number of invasive tests but possibly increased the number of preterm and cesarean deliveries.