Possible association of folic acid supplementation during pregnancy with reduction of preterm birth: a population-based study.

OBJECTIVE: Periconceptional folic acid or multivitamin supplementation is recommended for prospective pregnant women to prevent neural-tube defects. The question is whether it is worth continuing these supplementations after the first trimester of pregnancy or not. Thus the possible fetal growth promoting and/or preterm birth reducing effect of vitamin supplements in the second and mainly in the third trimester was studied. STUDY DESIGN: Comparison of birth outcomes of singletons born to primiparous pregnant women with prospectively and medically recorded vitamin supplement in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996 contained 6293, 169, and 311 primiparae with folic acid alone, multivitamins and folic acid+multivitamin supplementation, respectively, and their data were compared to the data of 7319 pregnant women without folic acid and folic acid-containing multivitamin supplementation as reference. RESULTS: Mean gestational age was 0.3 week longer and mean birth weight was by 37 g higher in the group of folic acid alone, than in the reference group (39.2 weeks; 3216 g). The rate of preterm births (7.6%) was significantly lower compared with the reference sample (11.8%), but the rate of low birth weight newborns did not show significant reduction. Folic acid alone in the third trimester associated with 0.6 week longer gestational age and a more significant reduction in the rate of preterm births (4.8%). CONCLUSIONS: Minor increase in mean birth weight after high dose of folic acid supplementation during pregnancy would not be expected to result in too large babies; however, the significant reduction in the rate of preterm births may have great public health benefit.

Self-poisoning during pregnancy as a model for teratogenic risk estimation of drugs.

The results of animal investigations cannot be directly extrapolated to pregnant women. Clinical and analytical epidemiological studies for human teratogenic risks have many inherent methodological problems and their predictions must be regarded with caution. Evaluation of the potential teratogenicity of extremely large doses of drugs in self-poisoned pregnant women who attempted suicide offers a unique model for finding associations between congenital abnormalities and different drugs. All self-poisoned patients were cared for at a toxicological inpatient clinic in Budapest, between 1960 and 1993. Out of 1044 pregnant women identified from three different periods of the project, 19 died. Women who survived were visited at home to reveal birth outcomes, and their children were evaluated medically to identify congenital abnormalities and to estimate cognitive-behavioral status. The previous or subsequent children of these pregnant women were used as controls. In general, self-poisoned pregnant women were young (peak age was 18 to 20 years) and primiparous; 55% were unmarried and of lower socioeconomic status. Suicide attempts with drugs were most frequent in the fourth postconceptional week and second pregnancy month. Of 1044 self-poisoned pregnant women, 411 delivered live-born babies, of which 367 children (89.3%) were evaluated. The self-poisoning model appears to have several benefits (e.g., dose-response estimation) in comparison with other methods. It is suggested that an international monitoring system of self-poisoned pregnant women should be established to provide a larger database.

Phenolphthalein treatment in pregnant women and congenital abnormalities in their offspring: A population-based case-control study.

Phenolphthalein is frequently used laxative drug since 1930s, but the possible teratogenic effect of phenolphthalein was not checked in casecontrol eptedmiological study. In addition US Food and Drug Administration (FDA) declared the mutagenic and carcinogenic effect of phenolphthalein in 1999, thus we decided to evaluate the birth outcomes particularly congenital abnormalities (CAs) of newborn infants born to women treated with phenolphthalein during pregnancy. Cases with CA and their matched controls without CA born to mothers with phenolphthalein use during pregnancy were compared in the population-based large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Of 22,843 cases with CA, 191 (0.83%) while of 38,151 controls, 247 (0.64%) were born to mothers with phenolphthalein treatment (adjusted OR with 95% CI: 1.3, 1.0-1.5). The mean gestational week at delivery was somewhat longer in both the case (0.3 week) and control (0.2 week) groups while the mean birth weight was somewhat larger in cases (46 g) and controls (12 g) born to mothers with phenolphthalein treatment during the study pregnancy compared with mothers without phenolphthalein treatment. These differences were in agreement with the lower rate of preterm births and low birth weight in controls born to mothers with phenolphthalein treatment during pregnancy. The detailed analysis of different CA groups showed an association between maternal phenolphthalein treatment during pregnancy and a higher risk for Hirschsprung's disease (p = 0.01) based on 4 cases in the so-called other isolated CA-group. In conclusion phenolphthalein treatment in pregnant women associates with a higher risk for Hirschsprung's disease in their children, but this finding is only a signal which needs confirmation or rejection in other studies.

Maternal kidney stones during pregnancy and adverse birth outcomes, particularly congenital abnormalities in the offspring.

OBJECTIVE: The possible adverse birth outcomes, particularly congenital abnormalities (CAs) in pregnant women with kidney stones (KS) previously have not been evaluated; therefore, we decided to study this possible association. METHODS: The population-based data set of the Hungarian Case-Control Surveillance of CAs, 1980-1996, was used for this analysis. RESULTS: Of 22,843 newborns or fetuses with CAs, 69 (0.30%) had mothers with KS during pregnancy. Of 38,151 matched control newborns without any abnormalities, 147 (0.39%) had KS during pregnancy. KS were associated with an adjusted prevalence odds ratio (POR) with 95% CI of 0.8, 0.6-1.0 for CAs. A higher prevalence of maternal KS during the first trimester of pregnancy was not found in any CA group. There was no higher rate of preterm birth and low birthweight in the newborns of pregnant women with KS. CONCLUSIONS: There is no higher risk for adverse birth outcomes particularly CAs in the offspring of mothers with KS and related drug treatments during pregnancy.

Maternal urinary tract infection and related drug treatments during pregnancy and risk of congenital abnormalities in the offspring.

OBJECTIVE: The association between urinary tract infection (UTI) of pregnant women and preterm birth/low birthweight is known, but the possible association between UTI and congenital abnormalities (CAs) was evaluated rarely. Only one study showed an association with atrial septal defect, thus we decided to check this possible association. DESIGN: The population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA); most maternal UTIs were based on medically recorded data. SETTING The HCCSCA, 1980-1996, contained 22 843 newborns or fetuses with CAs and 38 151 matched controls, i.e. newborn infants without any HCAs. POPULATION: Hungarian informative offspring: live births, stillbirths and prenatally diagnosed malformed fetuses. METHODS: Case-control pair analysis. MAIN OUTCOME MEASURES: Twenty-five CA groups. RESULTS: A total of 1542 (6.75%) mothers in the case group had UTI during entire pregnancy compared with 2188 (5.74%) mothers in the control group (adjusted prevalence odds ratios [POR] with 95% CI: 1.15, 1.06-1.24). We did not find a higher prevalence of UTI during the second and/or third months of pregnancy in total case group (adjusted POR with 95% CI: 1.1, 0.9-1.2) and in any group of CAs including atrial septal defect type II. CONCLUSIONS: No evidence for the teratogenic effect of maternal UTI and related drug treatments during early pregnancy.

The possible preterm birth preventive effect of ampicillin during pregnancy.

OBJECTIVE: To study the possible association between oral ampicillin treatment during pregnancy and pregnancy complications, in addition to birth outcomes, particularly preterm birth. METHODS: We evaluated newborn infants without congenital abnormalities born to mothers with or without ampicillin treatment during pregnancy in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities. RESULTS: Of 38,151 newborn infants, 2,630 (6.9%) had mothers with ampicillin treatment during pregnancy. Some pregnancy complications, particularly preeclampsia, showed a higher prevalence in pregnant women with ampicillin treatment. Mean gestational age was slightly longer (0.2 week) but it resulted in a significant reduction in the prevalence of preterm birth (7.1 vs 9.3%; adjusted POR with 95% CI: 0.8, 0.7-0.9). The preterm birth preventive effect of ampicillin was most obvious after the use of the drug in the first trimester of pregnancy. Similar difference was not seen in the reduction of low birth weight. The rate of preterm birth was lower in newborn infants born to mothers with acute infectious diseases of both the genitourinary and respiratory systems if they were treated by ampicillin. CONCLUSIONS: Ampicillin treatment, particularly in the first trimester of gestation, can reduce the proportion of preterm birth in pregnant women with acute infectious diseases of the genitourinary and respiratory system.