NEONATAL DEATH OF THE MOTHER TREATED BY METHYLPHENOBARBITONE DUE TO EARLY MASSIVE PULMONARY HAEMORRHAGE PROBABLY CAUSED BY VITAMIN K DEFICIENCY

Prikazano je zrelo donošeno novorođenče koje je neposredno po porodu očitovalo masivno plućno krvarenje koje se ponovilo u dobi od 8 sati, nakon čega je dijete umrlo. Krvarenja je vjerojatno uzrokovano nedostatkom vitamina K zbog liječenja majke epileptičarke metilfenobarbitonom (Phemiton) u trudnoći, što je ona zatajila i u trudnoći i dolaskom u rodilište. S obzirom na brzi tijek zbivanja i masivno krvarenje, nije ustanovljeno postojanje koagulopatije, no prestanak krvarenja neposredno po porodu nakon primjene vitamina K može svjedočiti o njegovom nedostatku. Tek smo nakon smrti novorođenčeta od majke saznali da se četiri godine liječi metilfenobarbitonom u dozi od 400 mg dnevno. Poznato je da liječenje antiepilepticima može u novorođenčeta izazvati sekundarni rani oblik hemoragijske bolesti, koja se može manifestirati kao intrakranijalno, intratorakalno, intraabdominalno i krvarenje na mjestu insercije skalp elektrode, dok plućno krvarenje kao u našega bolesnika izuzetno je rijetko. Važno je da se u trudnoći provede prevencija ranog oblika hemoragijske bolesti novorođenčeta primjenom vitamina K majci od 36. tjedna nadalje, te da se odmah po porodu u novorođenčeta učine koagulacijski testovi koje se onda mora na odgovarajući način zbrinuti bilo primjenom vitamina K ili svježe smrznute plazme.A case of a very mature well-developed newborn which manifested massive pulmonary hemorrhage immediately after birth is presented. The hemorrhage repeated within 8 hours and the child died. The hemorrhage was probably caused by a vitamin K deficit due to the fact that his epileptic mother had been treated with methylphenobarbitone (Phemiton) during pregnancy. She had kept it secret during pregnancy and on admission to maternity hospital. Considering the rapid course of events and massive hemorrhage, a coagulopathy was not discovered, but as the bleeding stopped immediately following birth after vitamin K had been administered it can be a sign of its deficit. Not before the newborn’s death did we learn from the mother that for four years she had been treated with methylphenobarbitone taking a 400 mg dosage daily. It is well-known that the anti-epileptic drug treatment can, in newborns, cause a secondary early form of hemorrhagic disease, which can be manifested intracranially, intrathoracally, intra-abdominally and as a bleeding at the place of scalp electrode insertion. Pulmonary hemorrhage, like in our patient, appears exceptionally rarely. In order to prevent an early hemorrhage disease in pregnancy it is important to administer vitamin K to mother from 36th week onward, and to make coagulation tests immediately after birth. The child must be then cared for accordingly either by vitamin K or fresh frozen plasma administration

Prospektivno praćenje trudnica na monoterapiji lamotriginom u Hrvatskoj - predkoncepcijsko savjetovanje i praćenje lijekova

We prospectively surveyed 23 pregnant women with epilepsy on lamotrigine monotherapy and reported outcome of their pregnancies, including one fetal intrauterine death, one spontaneous abortion and two preterm deliveries. There were no congenital malformations in their offspring. Women with pregnancy planning and folic acid intake delivered babies with higher values of birth weight and birth length. There was large inter-patient variation during drug monitoring and in the need of dose adjustment. Individual approach to every woman and monotherapy with minimal effective lamotrigine dose with frequent drug monitoring enhances the possibility for successful pregnancy. The management of women with epilepsy should begin with pre-pregnancy counseling. Planned pregnancy enables periconceptional folic acid supplementation. Despite the small number of cases, these data indicate that lamotrigine treatment during pregnancy might be relatively safe. Larger prospective studies are needed to obtain adequate power for statistical analysis including long-term cohort studies.U ovoj studiji smo prospektivno pratili ishod trudnoće u 23 trudnice s epilepsijom koje su uzimale lamotrigin kao monoterapiju. Trudnoća je kod bolesnica rezultirala intrauterinom smrću djeteta u jednom slučaju. spontanim abortusom u jednom slučaju, te prijevremenim porodom u dva slučaja. Kod novorođenčadi nisu zabilježene kongenitalne malformacije. Žene koje su planirale trudnoću i uzimale folnu kiselinu rodile su djecu s višom tjelesnom masom i visinom. Postojala je velika različitost medu bolesnicama u praćenju doze lijeka te u potrebi za usklađivanjem doze. Veća je mogućnost uspješnog planiranja trudnoće ako se svakoj bolesnici pristupi individualno uz minimalnu djelotvornu dozu lijeka (lamotrigin). Liječenje trudnica treba započeti savjetovanjem prije začeća kada je moguće i pravodobno započeti s uzimanjem folne kiseline. Unatoč malom broju slučajeva podaci iz naše studije pokazuju kako liječenje lamotriginom tijekom trudnoće može biti relativno sigurno. Potrebne su veće prospektivne studije kako bi se postigla zadovoljavajuća statistička snaga dobivenih podataka

COMBINED ULTRASOUND-BIOCHEMICAL SCREENING OF FETAL TRISOMIA IN THE FIRST TRIMESTER AND DOUBLE BIOCHEMICAL SCREENING IN THE SECOND TRIMESTER AT NONRISK PREGNANCIES

Cilj rada: Usporediti uspješnost primjene probirnih testova aneuploidija u prvom i drugom tromjesečju trudnoće. Ispitanice i metode: Istraživanu skupinu činilo je 374 trudnica s kombiniranim ultrazvučno-biokemijskim testom u prvom, odnosno dvostrukim biokemijskim testom u drugom tromjesečju. Sve su trudnoće bile jednoplodne i urednog ishoda. U probiru prvog tromjesečja korišteni su biokemijski biljezi u serumu trudnica: plazmatski protein pridružen trudnoći (PAPP-A) i slobodna B-podjedinica humanog korionskog gonadotropina (slobodni B-hCG), uz ultrazvukom izmjerenu debljinu nuhalnog nabora (NT) i dužinu tjeme-trtica (CRL) u ploda. U dvostrukom biokemijskom probiru drugog tromjesečja korišteni su biokemijski biljezi: alfa-fetoprotein (AFP) i slobodni B-hCG, a gestacija je procijenjena prema ultrazvučnoj biometriji. Rezultati: Povećani ultrazvučno-biokemijski rizik trisomije 21 u 1. tromjesečju trudnoće ustanovili smo u 30 trudnica (8.0%). Od ukupnog broja, 70 ispitanica (18.7%) imalo je povećani rizik obzirom na biokemijske biljege u ¬prvom, odnosno njih 56 (15.0%) obzirom na biokemijske biljege u drugom tromjesečju trudnoće. Izvršeno je ukupno 30 postupaka amniocenteze. Od toga je u 19 trudnica (63.3%) indikacija postavljena na osnovi kombiniranog probirnog testa. Nadalje, amniocenteza je izvršena u 11 trudnica (28.2%) zbog povećanog rizika u dvostrukom biokemijskom probiru drugog tromjesečja. Udjel lažno-pozitivnih razultata u kombiniranom probiru prvog tromjesečja bio je statistički značajno niži, nego u biokemijskom probiru drugog tromjesečja (B2=12.02, p=0.0005). Ustanovili smo značajnu pozi¬tivnu povezanost log10 MoM slobodnog B-hCG između prvog i drugog tromjesečja (r2=0.403, p<0.0001). Nismo ustanovili značajnu povezanost između ostalih biokemijskih biljega u prvom, odnosno, drugom tromjesečju. Zaključak: Rezultati našeg istraživanja su pokazali značajno veću specifičnost ranog kombiniranog probirnog testa aneuploidija u odnosu na biokemijski probirni test u prvom, kao i u drugom tromjesečju. Mogućnosti izbora pojedinih probirnih testova trebale bi biti usklađene sa stavovima i potrebama samih trudnica, kao i sa smjernicama koje su preporučile nadležne institucije za fetalnu medicinuObjective: To evaluate the performance of screening tests for aneuploidy in the first and second trimesters of pregnancy in Croatian pregnant women. Study Design and Methods: Study population comprised 374 pregnant women who underwent the combined ultrasound-biochemical in the first and double-test in the second trimester of pregnancy, respectively. All were singleton pregnancies with normal outcomes. The first-trimester screening was performed combining serum markers, pregnancy associated plasma protein-A (PAPP-A) and free B-subunit of human chorionic gonado¬tropin (free B-hCG) with fetal nuchal translucency thickness (NT) and crown-rump length (CRL), measured by ultrasound. For the second-trimester screening, maternal serum alpha-fetoprotein and free B-hCG were used as biochemical markers in relation to fetal biometry diagnosed by ultrasound. Results: In 30 pregnant women (8.0%) elevated risk for trisomy 21 was found after combined ultrasound-biochemical screening. Out of total, 70 pregnant women (18.7%) were classified ’at risk’ on the basis of biochemical markers in the first and 56 (15.0%) in the second trimester. In 30 pregnant women amniocentesis was performed. In 19 cases (63.3%) the indication was elevated risk in the first-trimester combined test. In 11 women (28.2%) amniocentesis is recommended because of the elevated second-trimester biochemical risk. The proportion of false-positive results in combined first-trimester screening test was significantly lower than with second-trimester biochemical markers (B2=12.02, p=0.0005). We found the significant positive relationship between log10 MoM F B-hCG in the first and second trimester (r2=0.403, p<0.0001). There was no significant relationship between PAPP-A and second-trimester biochemical markers. Conclusion: Results of this preliminary study confirmed better specificity of the combined first-trimester screening in relation to biochemical screening in the second trimester of pregnancy. The decision and choice of the most appropriate screening test should consider woman’s personal attitude and preferences, as well as follow the guidelines recommended by the competent associations for the fetal medicine

Biochemical Screening of Fetal Aneuploidies and Neural Tube Defects by »Double-Test« in Croatia: A 10 Years’ Experience

The aim of the study is to investigate the efficiency of the second-trimester biochemical screening, with maternal serum alpha-fetoprotein (MS-AFP) and free b-subunit of human chorionic gonadotropin (free b-hCG), during the ten-year period. The study included 11,292 of pregnant women between the 15th and 18th gestational week, who underwent screening from November 1996 to December 2006. The risk for trisomy 21 and trisomy 18 were calculated by computer software, based on a model which generated the final risk for fetal aneuploidies from the pregnant woman’s a priori age risk and the likelihood ratio of the distribution of the biochemical markers, according to the second-trimester gestation. With the cut-off value of the final risk 1:250, the detection rate for trisomy 21 was 75% (21/28). In women less than or equal to 35, the detection was 57.1% (8/14) and 92.9% (13/14) in those over 35 years, respectively. The detection rate of trisomy 18 was 50% (2/4). The results confirmed that the implementation of double-test, as non-invasive screening for fetal aneuploidies, should be accepted as a complementary method of antenatal care