Very young and advanced maternal age strongly elevates the occurrence of nonchromosomal congenital anomalies: a systematic review and meta-analysis of population-based studies.

BACKGROUND: Nonchromosomal congenital anomalies (NCAs) are the most common cause of infant mortality and morbidity. The role of maternal age is well known, although the specifics are not thoroughly elucidated in the literature. OBJECTIVE: To evaluate the role of maternal age in the incidence of NCAs and to pinpoint age groups at higher risk to refine screening protocols. STUDY DESIGN: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines and Cochrane Handbook. Searches were performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. Population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women were included, without restrictions on age range, country, or comorbidities. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies. RESULTS: From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (risk ratio [RR]: 1.31, confidence interval [CI]: 1.07 -1.61), rising notably after>40 (RR: 1.44, CI: 1.25 -1.66). The latter changes to 1.25 (CI: 1.08 -1.46) if the co-occurrence of chromosomal aberrations is excluded. Specific anomalies like cleft lip/palate (>40, RR: 1.57, CI: 1.11 -2.20) and circulatory system defects (>40, RR: 1.94, CI: 1.28 -2.93) were significantly associated with advanced maternal age. Conversely, gastroschisis was linked to mothers <20 (RR: 3.08, CI: 2.74 -3.47). CONCLUSION: The study confirms that both very young and advanced maternal ages significantly increase the risk of NCAs. There is a pressing need for age-specific prenatal screening protocols to better detect these anomalies, especially considering the current trend of delayed childbearing. Further research is required to fully understand the impact of maternal age on the prevalence of rarer NCAs.

Association between human papillomavirus and preterm delivery: A systematic review and meta-analysis.

INTRODUCTION: The lifetime prevalence of human papillomavirus infection (HPV) is estimated to be around 80% and it is the most common sexually transmitted infection. Despite being well known for its oncologic relevance, it has been associated with adverse pregnancy outcomes, though available evidence is contradicting. Previous meta-analyses involved articles which based HPV infection on Pap smear results, leading to a significant source of bias. Therefore, we aimed to assess the burden of genetically proven HPV infection on adverse pregnancy outcomes. MATERIAL AND METHODS: In our meta-analysis, pregnant women tested for HPV DNA were only considered eligible. We conducted a systematic search in three major databases (PubMed, Embase, and CENTRAL) on September 22, 2023. Cohort, cross-sectional, and case-control studies were eligible for the analysis. The exposed group consisted of HPV-infected patients. We assessed the odds ratios (OR) with a confidence interval (CI) of 95%. In order to reduce the heterogeneity, we performed subgroup analyses based on different strains (high risk HPV, HPV 16/18, study design). The study was prospectively registered on PROSPERO (CRD42022370228). RESULTS: Our study involved 14 articles with 7008 women. A significant association was found between preterm delivery and HPV infection (OR: 1.94, CI: 1.31-2.87). No significant association was found when separately examining high-risk HPV-infected women (OR: 1.94, CI: 0.82-4.59), and HPV 16 or 18-infected women (OR: 2.08, CI: 0.50-8.63) in terms of preterm delivery. No significant association was found between spontaneous abortion and HPV infection (OR: 1.02, CI: 0.16-6.31). CONCLUSIONS: Our analysis indicates an association between HPV infection and preterm delivery. It is imperative that future studies consider confounding variables more comprehensively. Additionally, the global implementation of HPV vaccination programs holds significance not only in oncology but also in obstetrics.

Ranking the dietary interventions by their effectiveness in the management of polycystic ovary syndrome: a systematic review and network meta-analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common condition in women, characterised by reproductive and metabolic dysfunction. While dietary approaches have been evaluated as a first-line treatment for patients with PCOS, there is limited evidence to support preference for a specific dietary composition. This systematic review and network meta-analysis was performed with the objective of comparing different dietary interventions in terms of positive impact. Metformin, the currently preferred treatment, was also compared. METHODS: The latest systematic search was performed on the 20th of March, 2023. Eligible randomised controlled trials (RCTs) included patients with PCOS and compared the dietary approach with another intervention or a standard diet. Outcomes were expressed via anthropometric measurements and hormonal, glycemic, and lipid levels. The Bayesian method was used to perform a network meta-analysis and to calculate the surface under the cumulative ranking curve (SUCRA) values in order to rank the dietary interventions. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: 19 RCTs were identified, comprising data from 727 patients who were variously treated with 10 types of dietary interventions and metformin. The Dietary Approaches to Stop Hypertension (DASH) diet was the most effective in reducing Homeostatic Model Assessment of Insulin Resistance (SUCRA 92.33%), fasting blood glucose (SUCRA 85.92%), fasting insulin level (SUCRA 79.73%) and triglyceride level (SUCRA 82.07%). For body mass index (BMI), the most effective intervention was the low-calorie diet (SUCRA 84.59%). For weight loss, the low-calorie diet with metformin (SUCRA 74.38%) was the most effective intervention. Metformin produced the greatest reductions in low-density lipoprotein cholesterol (SUCRA 78.08%) and total testosterone levels (SUCRA 71.28%). The low-carb diet was the most effective intervention for reducing cholesterol levels (SUCRA 69.68%), while the normal diet (SUCRA 65.69%) ranked first for increasing high-density lipoprotein cholesterol levels. CONCLUSION: Dietary interventions vary in their effects on metabolic parameters in women with PCOS. Based on our results, the DASH diet is the most effective dietary intervention for treating PCOS. Registration PROSPERO ID CRD42021282984.

Maternal age is highly associated with non-chromosomal congenital anomalies: Analysis of a population-based case-control database.

OBJECTIVE: The role of maternal age in the development of non-chromosomal congenital anomalies (NCAs) is under debate. Therefore, the primary aim of this study was to identify the age groups at risk for NCAs. The secondary aim was to perform a detailed analysis of the relative frequency of various anomalies. DESIGN: National population-based study. SETTING: The Hungarian Case-Control Surveillance of Congenital Anomalies (CAs) between 1980 and 2009. POPULATION OR SAMPLE: A cohort of 31 128 cases with confirmed NCAs was compared with Hungary's total of 2 808 345 live births. METHODS: Clinicians prospectively reported cases after delivery. Data were analysed by non-linear logistic regression. Risk-increasing effect of young and advanced maternal age was determined by each NCA group. MAIN OUTCOME MEASURES: These were the total number of NCAs: cleft lip and palate, circulatory, genital, musculoskeletal, digestive, urinary, eye, ear, face, and neck, nervous system, and respiratory system anomalies. RESULTS: The occurrence of NCAs in our database was lowest between 23 and 32 years of maternal age at childbirth. The relative risk (RR) of any NCA was 1.2 (95% CI 1.17-1.23) and 1.15 (95% CI 1.11-1.19) in the very young and advanced age groups, respectively. The respective results for the circulatory system were RR = 1.07 (95% CI 1.01-1.13) and RR = 1.33 (95% CI 1.24-1.42); for cleft lip and palate RR = 1.09 (95% CI 1.01-1.19) and RR = 1.45 (95% CI 1.26-1.67); for genital organs RR = 1.15 (95% CI 1.08-1.22) and RR = 1.16 (95% CI 1.04-1.29); for the musculoskeletal system RR = 1.17 (95% CI 1.12-1.23) and RR = 1.29 (95% CI 1.14-1.44); and for the digestive system RR = 1.23 (95% CI 1.14-1.31) and RR = 1.16 (95% CI 1.04-1.29). CONCLUSION: Very young and advanced maternal ages are associated with different types of NCAs. Therefore, screening protocols should be adjusted for these risk groups.

Maternal factors in the origin of cleft lip/cleft palate: A population-based case-control study.

OBJECTIVES: Orofacial clefts are among the most common birth defects, with an estimated worldwide incidence of around 1.5-1.7 per 1000 live-born babies. The most frequent form of orofacial clefts is cleft lip with or without cleft palate (CL ± CP). The role of environmental factors in the development of clefts is unclear in most patients, thus the aim of this study was to estimate possible maternal risk factors in the origin of CL ± CP. MATERIALS AND METHODS: 1648 CL ± CP cases, 2654 matched controls and 57 231 population controls were evaluated from The Hungarian Case-Control Surveillance of Congenital Abnormalities. Maternal factors during the critical period in cases and controls were compared. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated in a multivariable conditional logistic regression model. RESULTS: Among socio-demographic data, we have found significant differences between maternal employment. The proportion of unskilled mothers (6.5%) were higher in the CL ± CP group than in controls (3.5%). Medically recorded maternal anaemia, excessive vomiting and threatened abortion were associated with a higher risk of CL ± CP. An elevated risk was also found in various acute illnesses such as influenza (OR: 2.4, 95% CI: 3.0-5.8), acute bronchitis (OR: 4.5, 95% CI: 1.6-12.6) and urinary tract infections (OR: 3.5, 95% CI: 2.0-6.0). Maternal migraine and essential hypertension occurred more frequently in the mothers of cases than in controls. CONCLUSION: The findings of this study suggest that maternal diseases and lifestyle factors during the first trimester play a significant role in the development of CL ± CP.

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

OBJECTS: 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. SETTING AND SAMPLE POPULATION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Paroxysmal supraventricular tachycardia in pregnant women and birth outcomes of their children: a population-based study.

The aim of the study was to estimate the possible association of pregnant women with paroxysmal supraventricular tachycardia (PSVT) with the possible risk for adverse birth outcomes, particularly different congenital abnormalities (CAs) in their children. Prospectively and medically recorded PSVT was evaluated in 103 pregnant women who later had offspring with CA (case group) and 149 pregnant women who later delivered newborn infants without CA (control group) and matched to cases in the population-based data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996. Of 252 pregnant women with PSVT, 115 (45.6%) had the onset of this condition before the study pregnancy, that is, their PSVT was a chronic condition, while the rest (N = 137) of PSVT was considered as new onset in the study pregnancy. The comparison of occurrence of PSVT in pregnant women who had offspring with different CA groups and in control mothers showed a higher risk for cardiovascular CAs (adjusted OR with 95% CI: 2.1, 1.1-3.8) explained mainly by secundum atrial septal defect. This association was confirmed in pregnant women with PSVT in the second and/or third gestational month, that is, critical period of cardiovascular CAs. In conclusion PSVT in pregnant women associates with a higher risk of secundum atrial septal defect in their children.

Birth Outcomes of Children Born to Women with Rheumatoid Arthritis.

AIM: The aim of the study was to estimate the possible risk of adverse birth outcomes of children born to mothers with rheumatoid arthritis (RA). METHODS: The dataset of large population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities from 1980-1996 was evaluated including 22,843 cases with congenital abnormalities and 38,151 matched controls without any defect. RESULTS: 36 cases (0.16%) had mothers with RA, while 68 controls (0.18%) were born to mothers without RA (OR=0.9, 95% CI=0.3-1.6). A higher risk for congenital abnormalities in the offspring of pregnant women with RA was not found. In fact there was a larger mean birth weight in the newborns without any defect of mothers with RA and it was associated with a somewhat lower rate of low birth weight. CONCLUSIONS: RA seems to have a beneficial effect not only for pregnant women but for their foetuses as well.

PARP inhibitor era in ovarian cancer treatment: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer. METHODS: This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression- free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals (95% CI). The random-effects model was applied in all analyses. RESULTS: In the meta-analysis, 16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in the total population (HR 0.34, CI 0.29-0.40), BRCA mutant (HR 0.24, CI 0.18-0.31), germline BRCA mutant (HR 0.23, CI 0.18-0.30), and BRCA wild-type cases (HR 0.50, CI 0.39-0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51-0.76) compared with chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers in the overall population (HR 0.46, CI 0.30-0.71) and the BRCAm population (HR 0.36, CI 0.29-0.44). Although the risk of severe AEs was increased by PARPi therapy compared to placebo in most settings investigated, these side effects were controllable with dose modification, and treatment discontinuation was required in the minority of cases. CONCLUSIONS: PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated.

Imiquimod Is Effective in Reducing Cervical Intraepithelial Neoplasia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Topical Imiquimod is an immune response modifier approved for the off-label use of vulvar intraepithelial neoplasia. We conducted this systematic review and meta-analysis to investigate the efficacy and safety of Imiquimod in treating cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)-positive patients. METHODS: The study was prospectively registered (CRD420222870) and involved a comprehensive systematic search of five medical databases on 10 October 2022. We included articles that assessed the use of Imiquimod in cervical dysplasia and HPV-positive patients. Pooled proportions, risk ratios (RRs), and corresponding 95% confidence intervals (CIs) were calculated using a random effects model to generate summary estimates. Statistical heterogeneity was assessed using I2 tested by the Cochran Q tests. RESULTS: Eight articles reported on 398 patients who received Imiquimod out of 672 patients. Among CIN-2-3 patients, we observed a pooled regression rate of 61% (CI: 0.46-0.75; I2: 77%). When compared, Imiquimod was inferior to conization (RR: 0.62; CI: 0.42-0.92; I2: 64%). The HPV clearance rate in women who completed Imiquimod treatment was 60% (CI: 0.31-0.81; I2: 57%). The majority of side effects reported were mild to moderate in severity. CONCLUSIONS: Our findings indicate that topical Imiquimod is safe and effective in reducing cervical intraepithelial neoplasia and promoting HPV clearance. However, it was found to be inferior compared to conization. Imiquimod could be considered a potential medication for high-grade CIN patients and should be incorporated into guidelines for treating cervical dysplasia.

Vitamin D and pre-eclampsia: original data, systematic review and meta-analysis.

BACKGROUND/AIMS: Vitamin D may protect from pre-eclampsia through influences on immune modulation and vascular function. To evaluate the role of vitamin D in the development of pre-eclampsia, we conducted a systematic review and meta-analysis including novel data from 2 large-scale epidemiological studies. METHODS: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched for prospective observational studies of association between vitamin D supplementation or status (measured by maternal 25-hydroxyvitamin D, 25(OH)D) with a subsequent risk of pre-eclampsia, or randomised controlled trials using vitamin D supplementation to prevent pre-eclampsia. The Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) and the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in meta-analyses with published studies. RESULTS: Mothers receiving vitamin D supplementation earlier in pregnancy had lower odds of pre-eclampsia [pooled odds ratios (OR) 0.81 and 95% confidence interval (CI) 0.75-0.87, p = 2.4 × 10(-8), 2 studies] in the meta-analysis of published studies with HCCSCA. The meta-analysis of published studies with ALSPAC suggested an association between higher serum 25(OH)D levels and a reduced risk of pre-eclampsia (pooled OR 0.52 and 95% CI 0.30-0.89, p = 0.02, 6 studies). Randomised trials of supplementation were suggestive of protective association (pooled OR 0.66 and 95% CI 0.52-0.83, p = 0.001, 4 studies). CONCLUSIONS: This study suggests that low maternal serum 25(OH)D concentrations increase pre-eclampsia risk and that vitamin D supplementation lowers this risk. The quality of evidence is insufficient to determine a causal association, which highlights the need for adequately powered clinical trials.

[Screening of trisomy 21 nowadays. Is maternal age so important?]. / A 21-es triszómia szurése napjainkban. Az anyai életkor valóban olyan fontos?

INTRODUCTION: Trisomy 21 is the most common chromosomal abnormality, therefore, screening and diagnosis of this disorder is in the centre of attention worldwide. An efficient screening method is the combined test based on maternal age, ultrasound signs, biochemical markers, and a risk ratio can be calculated based on these data. AIM: The aim of the authors was to determine the causes of missed prenatal diagnosis of Down's syndrome at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. METHOD: A retrospective study was carried out by collecting data from medical records of mothers who had delivered a newborn with Down's syndrome in the Department between 2008 and 2012. Each medical record was analyzed individually. RESULTS: In most cases the missed diagnosis of Down's syndrome occurred when the expectant mother failed to attend the first trimester screening or did not take the risk of invasive diagnostic procedures needed for fetal kariotyping. CONCLUSIONS: Analysis of fetal DNA circulating in maternal plasma can be a solution for those who refuse invasive fetal diagnostics. This test has high sensitivity and very low false positive rate. It has become available since the end of 2011 in the United States and, since the autumn of 2012, in Hungary, too. The test, however, is not reimbursed by national health insurance.

[Sentinel lymph node biopsy in pregnancy-associated breast cancer]. / Orszemnyirokcsomó-biopszia terhességi emlorákban.

The incidence of pregnancy-associated breast cancer is rising. Sentinel lymph node biopsy is the method of choice in clinically node negative cases as the indicated minimally invasive regional staging procedure. Some reports have linked radioisotope and blue dye required for lymphatic mapping to teratogenic effects, the idea of which has become a generalized statement and, until recently, contraindication for these agents was considered during pregnancy. Today, there are many published reports of successful interventions with low-dose 99mTc-labeled human albumin nanocolloid, based on dosimetric modeling demonstrating a negligible radiation exposure of the fetus. These results contributed to the seemingly safe and successful use of sentinel lymph node biopsy during pregnancy, though generally it can not replace axillary lymphadenectomy in the absence of high-quality evidence. The possibility of sentinel lymph node biopsy should be offered to pregnancy-associated early breast cancer patients with clinically negative axilla, and patients should be involved in the decision making following extensive counselling. This paper presents the successful use of sentinel lymph node biopsy with low-dose tracer during two pregnancies (in the first and third trimesters) and, for the first time in Hungarian language, it offers a comprehensive literature review on this topic. Orv. Hetil., 154(50), 1991-1997.

Fundamental role of folliculo-luteal function in recurrent miscarriage.

PURPOSE: To re-evaluate the role of folliculo-luteal function (FLF) in recurrent miscarriage (RM) on the basis of new hormonal diagnostic criteria. METHODS: A prospective, randomized, single-blinded, placebo-controlled study was carried out at 110 apparently healthy patients with three or more miscarriages not related to any presumable predisposing factors of RM were investigated. In the treatment group FLF was normalized preconceptionally. Women in the control group received placebo. FLF was regarded as physiological when the mean of three progesterone (P) values measured every second day between the 4th and 9th day after ovulation or before menstruation was 21.0 ± 2.0 ng/ml. RESULTS: A significant difference (p < 0.001) was found between the physiological and placebo groups in the occurrence of live births: 93 versus 56 %, pregnancy losses: 7 versus 44 %; premature delivery per births: 10 versus 57 %. Luteal mean P and estradiol values were significantly (p < 0.001) different in cases of spontaneous abortions and premature and mature deliveries, respectively (P: 14.6 ± 2.2, 20.2 ± 2.7, 27.6 ± 3.9 ng/ml). A strong and significant correlation (p < 0.001) was found between luteal mean P values and the duration of pregnancy (r = 0.85), as well as between the P means measured in the luteal phase and different parameters of the newborns: weight (r = 0.89), weight percentile (0.86) and length (0.73). Retrospective analysis of our data suggests that a luteal P mean value of 29.3 ± 2.9 ng/ml characterising patients with singular, mature, eutroph newborns seems to be the most favorable P value for successful reproduction in RM. CONCLUSION: Determining the oocyte quality and placentation, FLF quantitatively determines the outcome of pregnancy: its duration and different characteristics of the newborns in RM.

Vitamin supply in pregnancy for prevention of congenital birth defects.

PURPOSE OF REVIEW: After the short summary of history of primary prevention of neural tube defects by folic acid or folic acid-containing multivitamin supplementation during the periconception period, the three main unsolved problems are highlighted. RECENT FINDINGS: Both intervention trials and observational studies confirmed that this new primary preventive method is effective - beyond the prevention of neural-tube defects - in the reduction of the most common structural birth defects: congenital cardiovascular abnormalities. Nevertheless, this important progress in the field of congenital abnormalities is not appreciated appropriately. The periconception supplementation of both folic acid alone and folic acid-containing multivitamin is useful; however, the available data indicate the higher efficacy of multivitamins in the primary prevention of neural-tube defects and congenital cardiovascular abnormalities. The optimal dose of folic acid is not known though this knowledge would be necessary from both a scientific and practical aspect. SUMMARY: Periconception folic acid or folic acid-containing multivitamin supplementation has resulted in a breakthrough in the primary prevention of neural-tube defects, cardiovascular abnormalities and probably some other defects; however, extra efforts are necessary to eliminate folic acid or folic acid-containing multivitamin preventable congenital abnormalities.

Association between uterus uni/bicornis in pregnant women and postural deformities in their offspring.

OBJECTIVE: The objective of the investigation was to study the possible association between uterus uni- or bicornis in pregnant women and structural birth defects (ie, congenital abnormalities) in their offspring. STUDY DESIGN: There were 22,843 cases with congenital abnormality recorded in the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. These subjects were matched to 38,151 controls without any defect. Prevalence of medically recorded uterus uni/bicornis in the prenatal maternity logbook in the mothers of subjects with different congenital abnormalities and of their matched controls without any defect were compared. RESULTS: Fifty-seven (0.25%) subjects and 67 (0.18%) controls had mothers with uterus uni/bicornis. There was a significant association of uterus uni/bicornis in pregnant women with a higher risk of total group of congenital abnormalities (adjusted odds ratio, 1.5; 95% confidence interval, 1.1-2.2) explained mainly by a significantly higher risk of clubfoot and particularly postural deformity association in their children (adjusted odds ratio, 4.7; 95% confidence interval, 2.4-9.1). CONCLUSION: Pregnant women with a uni/bicornis uterus have a significantly higher risk of clubfoot and postural deformity association.

Chronic hypertension in pregnancy.

PURPOSE OF REVIEW: Chronic hypertension is frequent in pregnant women as well. The objective of this review is to evaluate the maternal characteristics, pregnancy complications and birth outcomes including congenital abnormalities of pregnant women with chronic hypertension by reviewing the results of published studies and mainly the data of the population-based data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. A second aim of the review is to examine the efficacy of antihypertensive drug treatments in the reduction of pregnancy-associated risks in women with chronic hypertension. RECENT FINDINGS: Pregnant women with treated chronic hypertension had a higher risk - beyond the well known pre-eclampsia and low birthweight newborns - of threatened abortion and preterm delivery, placental disorders and gestational diabetes. In addition a higher risk of hypospadias in one and of esophageal atresia/stenosis in another study was found in the children of pregnant women with chronic hypertension. These latter findings are signals which need confirmation or rejection in other studies. SUMMARY: The present antihypertensive treatments do not neutralize the harm of severe chronic hypertension in pregnant women and in their offspring, thus it is necessary to introduce more effective drug combinations for the treatment of pregnant women with severe chronic hypertension.

Successful operative management of an intact second trimester abdominal pregnancy with additional preoperative selective catheter embolization and postoperative methotrexate therapy.

BACKGROUND: Abdominal pregnancy is a rare condition that may lead to severe complications. CASE REPORT: The authors report the case of a 17-week intact abdominal pregnancy diagnosed in the course of an investigation of lower abdominal pain. Ultrasonography and MR examination revealed an intact abdominal pregnancy. Subsequent angiography was performed to occlude the supportive artery of the pregnancy by selective embolization. The pregnancy was terminated safely by laparotomy a day later. The placenta was left in the abdominal cavity because of the high risk of massive and often uncontrollable bleeding, and treatment with methotrexate was applied postoperatively. CONCLUSIONS: Preoperative embolization and the postoperative methotrexate therapy facilitate the safe surgical treatment of abdominal pregnancy.

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.

A possible association between maternal otitis media and ear defect in their offspring.

BACKGROUND: The possible association between otitis media in pregnancy (OMP) and structural birth defects, that is, congenital abnormalities (CAs), in their offspring has not been studied. METHODS: The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 and 1996, was evaluated. RESULTS: There were 58 (0.25%) and 55 (0.14%) of 22 843 cases and 38 151 controls with mothers who had OMP, respectively. There was association of OMP and a higher risk of ear CA. CONCLUSIONS: A possible explanation for the association of OMP with higher risk of ear CA may be some morphological deviation of the inner ear.