Identification and follow-up of pregnant women with platelet-type human platelet antigen (HPA)-1bb alloimmunized with fetal HPA-1a.

INTRODUCTION: Pregnant women negative for human platelet antigen 1a (HPA-1a) are at risk of alloimmunization with fetal HPA-1a antigen inherited from the father, and their offspring may develop fetal and neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to analyze the frequency of HPA-1a alloimmunization in pregnant Polish women, the feasibility of using maternal platelets for intrauterine transfusions in women subjected to diagnostic fetal blood sampling (FBS) and to discuss potential consequences of alloimmunization. MATERIAL AND METHODS: Fifteen thousand two hundred and four pregnant women were typed for HPA-1a; HPA-1a negative were screened for anti-HPA-1a. Alloimmunized women received specialist perinatology care; some of them were subjected to FBS, followed by transfusion of HPA-1a negative platelet concentrates (PC) prepared from maternal blood. RESULTS: Three hundred seventy-three (2.5%) women were HPA-1a negative, and 32 (8.6%) tested positively for anti-HPA-1a. Antibodies were detected in 22 women during pregnancy. Diagnostic FBS followed by PC transfusion was performed in 14 woman, who were platelet donors for their 16 unborn babies. Blood donations were tolerated well by the patients, and also intrauterine platelet transfusions were uneventful. Pharmacotherapy with intravenous immunoglobulins was implemented in 11/22 patients. CONCLUSIONS: HPA-1a negative women (ca. 2.5% of all pregnant patients) are at risk of alloimmunization with HPA-1a antigen and developing FNAIT. Alloimmunized women can be donors of platelets for their offspring providing removal of antibodies from PC. Owing to potential complications, special care should be taken if an alloimmunized woman was qualified as a blood or stem cell recipient.

Foetal goitrous hypothyroidism - easy to recognise, difficult to treat. Is combined intra-amniotic and intravenous L-thyroxine therapy an option?

INTRODUCTION: Foetal hypothyroidism negatively impacts somatic and neurological child development and can be the cause of serious obstetric and perinatal complications. We present a rare case of a large foetal dyshormonogenetic goitre, causing foetal neck hyperexten-sion, oesophageal compression, and cardiac high-output failure. MATERIAL AND METHODS: A foetal goitre complicated by cardiomegaly and polyhydramnios was diagnosed at 23 weeks of gestation (WG) on a routine ultrasonographic (US) assessment in a healthy nullipara. Foetal blood sampling was performed and a severe foetal hypothyroid-ism was diagnosed. Treatment was undertaken with an intra-amniotic followed by combined intra-amniotic and intravenous injections of L-thyroxine (L-T4). A total of 11 doses of L-T4 were administered between 24-37 WG to the foetus. RESULTS: A complete regression of foetal goitre, cardiomegaly, and polyhydramnios was observed. At 38 WG the patient delivered vagi-nally a male infant with mild hypothyroidism and no signs of goitre or cardiomegaly on postnatal US. Neurological development of the one year old baby is normal. CONCLUSIONS: The effective diminishing of serum TSH concentration and goitre size was reached after combined intra-amniotic and in-travenous L-T4 injections were given. L-T4 requirement in the foetus is equal to or above 15 µg/kg daily and should be given in weekly intervals due to its rapid metabolism by the foetus and by placental type 3 deiodinase. Intra-amniotic L-T4 administration may be inef-fective when a large goitre indisposes amniotic fluid swallowing by the foetus, so then the combined L-T4 injections into the umbilical vein and intra-amniotically in experienced hands seems to be a reasonable and effective option.

Early vesico-amniotic shunting - does it change the prognosis in fetal lower urinary tract obstruction diagnosed in the first trimester?

OBJECTIVES: The aim of the study was to assess the outcome of vesico-amniotic shunting performed before 16 weeks of pregnancy in fetuses with severe megacystis diagnosed in the first trimester of pregnancy. MATERIAL AND METHODS: Between January 2008 and October 2012 severe megacystis with the bladder length > 15 mm was diagnosed in 17 fetuses. The procedure of early vesico-amniotic shunting (VAS) was offered to 8 patients with presumably isolated LUTO. The procedure of VAS was performed in 6 fetuses. Before the intervention one or two procedures of vesicocentesis and urine analysis were performed. RESULTS: In all treated cases shunts provided urinary tract decompression. All babies were born prematurely, 2 of them died due to premaurity, 3 of them survived and have normal renal function at the age of 5-6 years. In 4/5 children accompanying malformations were later diagnosed, in 1 born prematurely neonate necropsy was not performed. CONCLUSIONS: Our results suggest that early vesico-amniotic shunting in fetal LUTO is feasible and may potentially prevent not only pulmonary hypoplasia but also renal insufficiency. However, the rationale of the procedure needs further investigation due to a high risk of long-term morbidity and co-existing malformations in children Before offering the therapy detailed counseling of the parents about the possible pros and cons of the therapy is necessary.

Ultrasound guided balloon catheterisation: a new method of fetal lower urinary tract obstruction management.

OBJECTIVES: Fetal lower urinary tract obstruction (LUTO), most often associated with presence of posterior urethral valves, poses high risk of perinatal mortality or postnatal renal failure. Looking for a method of causative treatment we have devel-oped a technique of fetal urethroplasty with a coronary angioplasty balloon catheter inserted under an ultrasonographic guidance via an 18-gauge needle introduced transabdominally to fetal bladder. MATERIAL AND METHODS: We have used this procedure in three women with singleton pregnancies (two primiparas and one multipara, 32-35 years of age), diagnosed with fetal megacystis at 12-16 weeks of gestation. Urethral catheterization was carried out at 16-18 weeks and an unobstructed urine flow was achieved in all three cases immediately after the procedure, followed by a resolution of megacystis and normalization of amniotic fluid volume. RESULTS: In all three cases, the post-procedure period was uneventful. In the first two fetuses, amniotic fluid volume re-mained normal until 30 weeks of gestation when a gradual development of oligohydramnios and some signs of renal cystic dysplasia were observed. Nevertheless, both pregnancies were continued till term (37 and 39 weeks, respectively) and two boys without signs of pulmonary hypoplasia were delivered. The third patient is currently 25 weeks pregnant; volume of amniotic fluid in her fetus is normal and no signs of urinary flow obstruction or renal dysplasia have been recorded thus far. CONCLUSIONS: Although some technical aspects of the procedure still need to be established, it seems worth consideration as a form of potentially least traumatic intrauterine intervention in fetuses with lower urinary tract obstruction.

Intrapartum sonography - eccentricity or necessity?

Ultrasonography has been extensively used in obstetrics and gynecology since 1980's. It found application in pediatric gynecology, procreation period, post-menopause, pregnancy monitoring and after delivery. Although the first reports on the use of ultrasonography in assessing delivery mechanism were published in 1990's, yet to date labor progress is evaluated by means of physical examination in most delivery units. Intrapartum sonography is not routinely performed despite the fact that numerous studies documented high error rates of conventional obstetrical examination. Even an experienced physician makes a mistake in every third case of the fetal head descent and fontanelle position assessment. Nowadays, obstetrician's role is not to strain for vaginal delivery at all costs, but to provide the patient in labor and her newborn with maximal safety. To achieve this objective, an obstetrician should distinguish between women who will deliver spontaneously and whose who require Cesarean section. Proper decision should be made on the basis of objective and valid evaluation of obstetric setting, which cannot be achieved solely with physical examination. Intrapartum sonography was shown to be far more accurate than digital examination. Moreover, it is not technically demanding, provides high reproducibility and neither increases the rate of ascending infection or causes discomfort to the patient. Current research suggests that if used routinely, intrapartum sonography can increase the safety of labor and reduce cesarean section rate.

[Fetal cardiac interventions - are we ready for them?]. / Interwencyjne zabiegi kardiologiczne u plodów - czy jestesmy do nich przygotowani?

OBJECTIVE: The aim of the study was to analyze types and methods of intrauterine fetal cardiac interventions performed between June 2011 and December 2013, and to assess the perinatal management of the neonates. METHODS: The program was developed after analysis of the available literature, practical individual training in Linz, Austria, and simulation of the procedure in a dissecting-room. The rules for anesthesia in pregnant women and their fetuses were developed. The interventions were performed in fetuses with critical cardiac defects, in the operating room, under ultrasonographic control. The protocol was approved by the Local Bioethics Committee at the Centre of Postgraduate Medical Education. MATERIAL: We included fetuses with critical aortic stenosis (n=29), critical pulmonary stenosis (n=2), and closed or extremely restricted foramen ovale (n=7). Between June 2011 and December 2013, the team comprised of JD, MD and AK conducted 42 interventions in 35 fetuses, including 32 balloon aortic valvuloplasties (in 29 fetuses), 2 pulmonary valvuloplasties, 4 balloon atrial septostomies and 4 atrial septal stent placement. Three fetuses required both, aortic valvuloplasty and fenestration of the atrial septum. RESULTS: Out of the 42 procedures, 41 (97%) were technically successful. We recorded 3 cases of fetal demise associated with the intervention. We modulated the protocol of anesthesia given to pregnant women, switching from general to local anesthesia with intravenous sedation. We always provided additional fetal anesthesia with fentanyl and atracurium via the umbilical vein. CONCLUSIONS: Based on our 2.5-year experience, it seems safe to conclude that all types of fetal cardiac interventions may be successfully conducted at Polish centers. The procedures are safe for the pregnant women and improve fetal status. Most of the neonates treated prenatally were referred in good general condition to a tertiary pediatric cardiology and cardiac surgery center

Hyperthyroidism during pregnancy--the role of measuring maternal TSH receptor antibodies and foetal ultrasound monitoring.

INTRODUCTION: To evaluate the usefulness of measuring maternal anti-TSH receptor antibodies (TRAbs) and foetal ultrasound (US) monitoring in cases of current or past maternal hyperthyroidism. MATERIAL AND METHODS: 77 pregnant women suffering from hyperthyroidism or with a history of Graves' hyperthyroidism were observed prospectively. Maternal serum TSH, fT4, fT3, TRAbs, and foetal US were performed at baseline and repeated every 2-4 weeks when needed. Neonatal thyroid status was assessed based on serum TSH, fT4 and fT3 obtained in the first days of life. RESULTS: 35 women were diagnosed with gestational hyperthyroidism and 42 with Graves' disease; among them 26 had current and 16 past hyperthyroidism. Foetal and neonatal thyroid dysfunction occurred only in cases of maternal Graves' disease: nine (21%) and three (7%), respectively. Active maternal Graves' hyperthyroidism and TRAbs elevated at least five times above the upper normal limit predisposed to foetal hyperthyroidism. Maternal anti-thyroid drug therapy (ATD) and low TRAbs and fT4 were the risk factors of foetal hypothyroidism. Abnormal foetal thyroid sonogram was the only sign of foetal thyroid dysfunction. Four patients (9.5%) had high TRAbs in the 3rd trimester (10.8-29.9 IU/mL), but neither foetal nor neonatal thyroid dysfunctions were noted. CONCLUSIONS: In the cases of maternal Graves' disease, foetal thyroid dysfunction occurs more often than commonly assumed. Foetal thyroid US is a valuable tool in early diagnosis and monitoring of the foetal thyroid status in pregnancy complicated by maternal Graves' disease. The evaluation of biological activity of maternal TRAbs may be helpful in prenatal diagnosis in some cases.

Increased size and vascularisation, plus decreased echogenicity, of foetal thyroid in two-dimensional ultrasonography caused by maternal Graves' disease.

Foetal ultrasonography monitoring is a valuable tool in assessing foetal thyroid function when pregnancy is complicated by maternal Graves' disease with accompanying high levels of TSH receptor antibodies, or when antithyroid drug therapy is instituted. Among several ultrasonographic signs of foetal thyroid disorder such as abnormalities in bone maturation and heart rhythm, cardiac failure, hydrops, intrauterine growth restriction and polyhydramnios, goitre is the most sensitive one. Here we report three cases of pregnant women with Graves' disease accompanied by very high serum levels of TSH receptor antibodies. In all three cases, as documented by foetal or neonatal serum TSH and thyroid hormones measurements, foetal thyroid dysfunction occurred. The only ultrasonographic sign of foetal involvement was a goitre with decreased echogenicity and increased vascularisation, central or peripheral. This is the first report demonstrating that a foetal thyroid gland when affected by transplacental passage of maternal TSH receptor stimulating antibodies can present exactly the same characteristic ultrasound pattern of Graves' disease as in adults.

Successful intrauterine treatment and good long-term outcome in an extremely severe case of fetal hemolytic disease.

A 34-year-old multiparous woman presented with anti-Rh-D antibodies (1: 512) and fetal hydrops at the 21(st) week of gestation. Ultrasound revealed massive fetal skin edema, ascites, hepatomegaly, placentomegaly, and anhydramnios. No fetal movements were observed. Fetal heart was enlarged, with reportedly decreased contractibility. The Doppler parameters were abnormal: the peak systolic velocity in median cerebral artery (MCA PSV) was increased (84 cm/s, 3 MoM), and absent end diastolic flow (AEDF) was reported in the umbilical artery. Ultrasound examination indicated severe fetal anemia and heart failure. Umbilical vein puncture was performed and the fetal blood count was determined (RBC 0.01 × 10(6)/µl, Ht 0.1%, PLT 67 × 10(3)/µl, WBC 2.1 × 10(3)/µl, indeterminable hemoglobin level). Packed red blood cells (0 Rh-, 30 ml) were immediately transfused to the fetus. Altogether, seven intrauterine transfusions were performed. Fetal hydrops disappeared gradually during the next few weeks. The male neonate (1860 g, 45 cm, Apgar score 3-4) was delivered after the last transfusion at 34(th) week of gestation due of intrauterine asphyxia. The infant was discharged after 21 days, in good condition, on breastfeeding. There was one 10 mm focus of periventricular leukomalacia in the brain, diagnosed based on trans-fontanel ultrasound, without any signs of damage to other organs. At the age of 5 years, the child is healthy, with no abnormalities in his neurodevelopmental parameters.

Fetal thyroid in two-dimensional ultrasonography: nomograms according to gestational age and biparietal diameter.

OBJECTIVE: To establish fetal thyroid nomograms based on gestational age and biparietal diameter and to compare obtained results with previously published data. STUDY DESIGN: A cross-sectional study of 241 healthy pregnant women at 14-38 week of gestation was undertaken. Exclusion criteria were: known maternal thyroid or systemic disease, unknown date of last menstrual period, multiple pregnancy and fetal malformations. Fetal thyroid diameter (FTD), circumference (FTC) and area (FTA) were measured by two-dimensional ultrasonography and plotted against gestational age (GA) and biparietal diameter (BPD). RESULTS: FTD, FTC and FTA increased logarithmically to GA and BPD. Fetal thyroid measurements as a function of GA were expressed by logarithmic formulas: ln(FTD)=3.6025-23.0315/GA, ln(FTC)=4.6227-22.8003/GA, ln(FTA)=6.6303-45.0831/GA. The following logarithmic formulas were obtained for fetal thyroid measurements according to BPD: ln(FTD)=3.4068-45.4271/BPD, ln(FTC)=4.4271-44.8359/BPD, ln(FTA)=6.2390-88.4408/BPD. There were highly significant correlations between thyroid measurements and GA or BPD: r=0.87-0.90, p<0.00001. CONCLUSIONS: We have established age-dependent and age-independent nomograms of fetal thyroid. These nomograms will enable prenatal diagnosis in fetuses at risk of thyroid disorders.

[The first successful fetal aortic balloon valvuloplasty in Poland]. / Pierwsza w Polsce skuteczna przezskórna plastyka balonowa zastawki aortalnej u plodu.

Prenatal aortic valvuloplasty is performed only in few perinatal centers in the world. Critical aortic stenosis which can lead to hypoplastic left heart syndrome or severe fetal heart failure with nonimmune hydrops is an indication for this procedure. Prenatal intervention can change the natural course of the disease. Authors present the first successful fetal balloon aortic valvuloplasty in Poland. It was performed in a 29-week fetus with critical aortic stenosis, severe impairment of left ventricular function, heart failure and fetal hydrops. After successful intervention, without any complications, left ventricular function and fetal condition improved gradually Effective fetal intervention was possible after few months of preparation and building a team of specialists. This is the first successful fetal cardiac intervention in Poland, which opens the way to the new era of fetal cardiology and hopefully will lead to improve results in children with this critical heart defect.

Iodine status of pregnant women from central Poland ten years after introduction of iodine prophylaxis programme.

INTRODUCTION: Until 1997, Poland was one of the European countries suffering from mild/moderate iodine deficiency. In 1997, a national iodine prophylaxis programme was implemented based on mandatory iodisation of household salt with 30 ± 10 mg KI/kg salt, obligatory iodisation of neonatal formula with 10 µg KI/100 mL and voluntary supplementation of pregnant and breast-feeding women with additional 100-150 µg of iodine. Our aim in this study was to evaluate the iodine status of pregnant women ten years after iodine prophylaxis was introduced. MATERIAL AND METHODS: A cross-sectional study was undertaken in 100 healthy pregnant women between the fifth and the 38th week of gestation with normal thyroid function, singleton pregnancy, normal course of gestation, without drugs known to influence thyroid function except iodine. Serum TSH, fT(4), fT(3), thyroglobulin (TG), anti-peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (TGAb) and urinary iodine concentration (UIC) were determined. Thyroid volume and structure were evaluated by ultrasonography. RESULTS: Fifty nine per cent of studied pregnant women had a diet rich with iodine carriers and 35% obtained iodine supplements. Twenty eight per cent appeared to have a goitre: 11 diffuse and 17 a nodular one, median goitre volume was 18.7 mL (range 6.8-29.0 mL). Median UIC was 112.6 µg/L (range 36.3-290.3 µg/L), only 28% of women had UIC ≥ 150 µg/L. Median UIC was significantly higher in the group receiving iodine supplements than in the group without iodine supplements: 146.9 µg/L v. 97.3 µg/L respectively, p 〈 0.001. Serum TSH, fT(3) and fT(3)/fT(4) molar ratio increased significantly during pregnancy while fT(4) declined. Median serum TG was normal: 18.3 ng/mL (range 0.4-300.0 ng/mL) and did not differ between trimesters. Neonatal TSH performed on the third day of life as a neonatal screening test for hypothyroidism was normal in each case: median value was 1.49 mIU/L (range 0.01-7.2 mIU/L). Less than 3% (2 out of 68) of results were 〉 5 mIU/L. CONCLUSION: Iodine supplements with 150 µg of iodine should be prescribed for each healthy pregnant woman according to the assumptions of Polish iodine prophylaxis programme to obtain adequate iodine supply. (Pol J Endocrinol 2010; 61 (6): 646-651).