Association of drug treatments in pregnant women with the risk of external ear congenital abnormalities in their offspring: a population-based case-control study

The objective of this study was to evaluate the possible association of drug treatments in pregnant women with a higher risk of congenital abnormalities of the external ear, particularly microtia/anotia, in their children. The frequency of drug treatments was compared in the mothers of cases with isolated or multiple (syndromic) ear abnormalities and in the mothers of three different controls: controls matched to cases, all controls (these controls had no defects) and malformed controls in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. There was no significantly higher use of any drug in the mothers of 354 cases with isolated external ear abnormalities than in the mothers of different controls. However, of 156 cases with multiple ear abnormalities, 11 had mothers with hydroxyethylrutosidea treatment and a characteristic pattern of congenital abnormalities was found in these children. Four cases with multiple ear abnormalities were born to epileptic mothers treated with valproate, phenytoin and polytherapy in two cases. Drug treatments are not important in the origin of isolated ear abnormalities. However, a higher risk of multiple ear abnormalities was found in children born to mothers with treatment of hydroxyethylrutosidea or antiepileptic drugs during pregnancy

Sex ratio of newborn infants born to pregnant women with severe chronic constipation

There was a significant male excess in the newborns of pregnant women with severe chronic constipation during pregnancy compared to pregnant women without constipation and pregnant women with new onset severe constipation, during pregnancy

A study of the risk of mental retardation among children of pregnant women who have attempted suicide by means of a drug overdose

BACKGROUND: The aim of the study was to estimate the effect on the fetal development of high doses of prescription drugs taken as a suicide attempt during pregnancy. METHODS: Pregnant women were identified among self-poisoned females in the toxicological inpatient clinic in Budapest between 1960 and 1993. Congenital abnormalities, intrauterine development based on birth weight and post-conceptional age, mental retardation, cognitive-behavioral status were compared in exposed children born to mothers who had attempted suicide by means of a drug overdose during pregnancy with their siblings, born either before or after the affected pregnancy, as sib controls. RESULTS: Of a total of 1 044 pregnant women, 74 used the combination of amobarbital, glutethimide and promethazine (Tardyl®, one of the most popular drugs for treatment of insomnia in Hungary) for suicide attempt. Of these 74 women, 27 delivered live-born babies. The mean dose of Tardyl® used for suicide attempts was 24 times the usually prescribed clinical dose. The rate of congenital abnormalities and intrauterine retardation was not higher in exposed children than in their sib controls. However, of the 27 exposed children, eight (29.6%) were mentally retarded (Χ21=79.7, p= Sig) while mental retardation did not occur among 46 sib controls. These exposed children were born to mothers who attempted suicide with Tardyl® between the 14th and 20th post-conceptional weeks. The components of Tardyl® used separately for a suicide attempt during pregnancy were not associated with a higher risk of mental retardation. Therefore the high doses of Tardyl® associated with the high risk for mental retardation may be due to the interaction of its three drug components. CONCLUSIONS: The findings of the study showed that the high doses of a drug containing three components may be associated with a significantly increased risk for mental retardation without any structural defects, whereas each of these three component drugs taken alone was not associated with this adverse effect

Birth Outcomes of Newborns after Folic Acid Supplementation in Pregnant Women with Early and Late Pre-Eclampsia: A Population-Based Study

Objective. To evaluate the rate of preterm birth and low birth weight in the newborns of pregnant women with early and late onset pre-eclampsia according to folic acid supplementation. Study design. Birth outcomes of newborns were evaluated in 1,017 (2.7%) pregnant women with medically recorded pre-eclampsia and 37,134 pregnant women without pre-eclampsia as reference in the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980–1996, in addition these study groups were differentiated according to the supplementation of high dose of folic acid alone from early pregnancy. Results. Pregnant women with pre-eclampsia associated with a higher rate of preterm birth (10.2% versus 9.1%) and low birthweight (7.9% versus 5.6%). There was a lower risk of preterm birth (6.8%) of newborn infants born to pregnant women with early onset pre-eclampsia after folic acid supplementation from early pregnancy though the rate of low birthweight was not reduced significantly. There was no significant reduction in the rate of preterm birth and low birthweight in pregnant women with late onset pre-eclampsia after folic acid supplementation. Conclusion. The rate of preterm birth in pregnant women with early onset pre-eclampsia was reduced moderately by high doses of folic acid supplementation from early pregnancy

Maternal-related factors in the origin of isolated cleft palate-A population-based case-control study

Isolated cleft palate (CPO) is the rarest form of oral clefting affecting 1-25 per 10 000 newborns worldwide. There is increasing evidence for the different pathogenetic backgrounds of CPO and cleft lip with or without cleft palate. The role of environmental factors in the origin of non-syndromic and syndromic CPO is unclear in most patients. The aim of this study was to estimate possible maternal risk factors in the origin of CPO.The Hungarian Case-Control Surveillance of Congenital Abnormalities contains data of 32 345 birth defect cases and 57 231 control newborns. The study samples included 751 cases with isolated CPO, 1196 matched controls and 57 231 population controls.Maternal diseases during pregnancy in cases and population controls were compared, and adjusted ORs with 95% CI were calculated in a multivariable unconditional logistic regression model.Beyond the well-known robust female excess (58.9%)-maternal smoking (OR with 95% CI: 2.34, 1.94-2.81) medically recorded maternal anaemia, threatened abortion and excessive vomiting in pregnancy were associated with a higher risk for CPO in the offspring. An elevated risk was found in Graves' disease (OR: 4.30, 1.74-10.62), epilepsy (OR: 4.64, 2.44-8.82), migraine (OR: 2.82, 1.18-6.76) and essential hypertension (OR: 2.33, 1.32-4.10). Among acute diseases common cold (OR: 4.94, 3.48-7.03), acute respiratory infections (OR: 4.20, 1.49-11.82), influenza (OR: 2.95, 1.75-4.95), pulpitis (OR: 7.85, 2.80-22.03), cholecystitis (OR: 3.15, 1.16-8.60), acute urinary tract infections (OR: 4.08, 2.22-7.49) and pelvic inflammatory diseases (OR: 3.93, 1.62-9.53) during pregnancy also were associated with an increased risk for developing CPO.The findings of this study suggest that maternal diseases and lifestyle factors during the first trimester play a significant role in the development of isolated cleft palate

A várandósság alatti emlőrák kezelése = Treatment of pregnancy associated breast cancer

Terhességi emlőráknak a várandósság ideje alatt, illetve a szülést követő egy éven belül kialakuló rosszindulatú emlődaganatot nevezzük. Háromezer várandós nőből körülbelül 1-ben alakul ki. A tumor incidenciája növekedő tendenciát mutat, amelyben elsősorban a gyermekvállalás egyre későbbi életkorra való kitolódása játszhat szerepet. A várandós állapot késlekedést okozhat mind a diagnózis felállításában, mind a megfelelő kezelés elindításában. Közleményünkben egy 30 éves nőbeteg esetét ismertetjük, aki első terhességének 21. hetében önvizsgálat során észlelte a jobb emlő bőrének gyulladásos elváltozását, és a hónaljárokban levő megnagyobbodott nyirokcsomókat. Az antibiotikus kezelésre a páciens panaszai nem javultak, ezért az axillaris képlet vékonytű-aspirációs citológiai vizsgálatát végezték el, amelynek során metasztatikus emlőrák igazolódott. A klinikánkon végzett vizsgálat során cT4 cN3 lokoregionális kiterjedésű daganatot véleményeztünk. Az emlő bőrének elváltozása gyulladásos emlőrákra utalt, emellett axillaris, valamint supraclavicularis nyirokcsomó-konglomerátumot is tapintottunk. A core-bioptátum értékelése során hormonreceptor-negatív, Her-2-pozitív, grade III differenciáltságú invazív carcinoma igazolódott. Neonatológiai és onkológiai konzíliumot követően a beteg úgy döntött, hogy a várandósság alatt elzárkózik a kemoterápiás kezeléstől, ezért a 30. gesztációs héten elektív császármetszést végeztünk. A további vizsgálatok távoli áttétet nem igazoltak, így primer szisztémás kemoterápiát kezdtünk, majd ezt követően mastectomia és axillaris blokkdisszekció történt. Az eltávolított emlőállományban visszamaradt tumort a kórszövettani vizsgálat során már nem azonosítottunk, a szöveti kép alapján komplett patológiai remissziót véleményeztünk. A sugárkezelés befejezése után trastuzumabkezelést indítottunk. Az ellenőrző vizsgálatok a páciensnél eddig sem helyi kiújulást, sem távoli áttétet nem igazoltak. Az újszülött generalizált izomtónus-eloszlási zavarok miatt jelenleg is fejlődésneurológiai gondozás alatt áll. | Pregnancy-associated breast cancer (PABC) is defined as cancer of the breast diagnosed during pregnancy and up to 1 year postpartum. The crude incidence is 1/3000 pregnant women. As women delay childbearing the incidence of PABC increases with age. Young patients with PABC do not have worse prognosis compared with those with non-PABC; however, pregnancy can contribute to a delay in breast cancer diagnosis, evaluation, and treatment. Primary care physicians and gynecologists should be careful in the thorough workup of breast symptoms in the pregnant population to expedite diagnosis and allow multidisciplinary treatment as early as possible following the established diagnosis. Authors report a case of a 30-year-old pregnant woman, who detected inflammatory signs of her right breast and a palpable axillary mass at the 21st week of gestation. Her symptoms did not improve with administration of antibiotics. Therefore fine needle aspiration biopsy of the axillary lump was performed, with the result of unequivocal diagnosis of metastatic invasive carcinoma. The patient was referred to the multidisciplinary tumor board of our Department at the 27st week of gestation with the symptoms of inflammatory breast cancer, palpable right axillary and supraclavicular lymph nodes. Core biopsy showed an ER and PR negative, Her-2 positive, grade 3, infiltrating ductal carcinoma of the breast. After multidisciplinary team consultation the patient declined any kind of therapy during her pregnancy. On the 30th week of gestation caesarean section was performed. The premature baby girl was treated in the Neonatal Intensive Care Unit. Imaging modalities revealed no evidence of distant metastases short after the delivery. After 6 cycles of chemotherapy (docetaxel-doxorubicin-cycclophosphamid) the patient underwent right mastectomy and axillary lymph node dissection. Complete pathological response was diagnosed, since no residual tumor was found in the surgical resection specimen. After radiotherapy, trastuzumab medication was initiated. To date, there is no evidence of local recurrence or distant metastases during her 24 months follow-up. The newborn is on close neurohabilitation folow-up due to the evidence of generalized muscle dystonia. Had the patient accepted chemotherapy, the damage of the newborn baby would have been avoidable

Prevention of Neural-Tube Defects with Periconceptional Folic Acid, Methylfolate, or Multivitamins?

Background/Aims: To review the main results of intervention trials which showed the efficacy of periconceptional folic acid-containing multivitamin and folic acid supplementation in the prevention of neural-tube defects (NTD). Methods and Results: The main findings of 5 intervention trials are known: (i) the efficacy of a multivitamin containing 0.36 mg folic acid in a UK nonrandomized controlled trial resulted in an 83-91% reduction in NTD recurrence, while the results of the Hungarian (ii) randomized controlled trial and (iii) cohort-controlled trial using a multivitamin containing 0.8 mg folic acid showed 93 and 89% reductions in the first occurrence of NTD, respectively. On the other hand, (iv) another multicenter randomized controlled trial proved a 71% efficacy of 4 mg folic acid in the reduction of recurrent NTD, while (v) a public health-oriented Chinese-US trial showed a 41-79% reduction in the first occurrence of NTD depending on the incidence of NTD. Conclusions: Translational application of these findings could result in a breakthrough in the primary prevention of NTD, but so far this is not widely applied in practice. The benefits and drawbacks of 4 main possible uses of periconceptional folic acid/multivitamin supplementation, i.e. (i) dietary intake, (ii) periconceptional supplementation, (iii) flour fortification, and (iv) the recent attempt for the use of combination of oral contraceptives with 6S-5-methytetrahydrofolate (methylfolate), are discussed. Obviously, prevention of NTD is much better than the frequent elective termination of pregnancies after prenatal diagnosis of NTD fetuses

Possible multifactorial etiology of isolated microtia/anotia-A population-based study

Objective: To test the possible multifactorial-threshold model in the origin of isolated microtia/anotia (IMA). Method: The observed number of IMA in the first degree relatives of cases affected was compared with the expected number of affected first degree relatives based on the multifactorial-threshold model in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Results: Of 354 cases with IMA, 14 (4.0%) had the affected first degree relatives with IMA. There was a low and similar rate of familial occurrence of IMA in parents and siblings of cases. The observed numbers of affected first degree relatives of cases with IMA and their expected numbers did not show significant difference (p= 0.47). Some other findings (e.g. male excess and the interaction of triggering environmental factors with polygenic predisposition) confirmed this hypothesis. Conclusions: The familial pattern of cases with IMA does not reject the hypothesis that the multifactorial-threshold model, i.e. gene-environmental interaction, may be the explanation for the origin of this congenital abnormality group, although the number of familial cases was quite small in the study. © 2011 Elsevier Ireland Ltd