Serial examination of 20,248 newborn fetuses and infants: Correlations between drug exposure and major malformations

Queißer‐Luft, Annette; Eggers, Inez; Stolz, Gabriela; Kieninger‐Baum, Dorothee; Schlaefer, Klaus

doi:10.1002/(sici)1096-8628(19960503)63:1<268::aid-ajmg45>3.3.co;2-z

Cited by 11 publications

(15 citation statements)

References 20 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4,5,8,31 Overall, our findings are consistent with the majority of previous studies that found no increase in the risk of most congenital defects among mothers taking OCs immediately before or after conception. [2][3][4][5][6][7][8][9][10][11][12] Given the multiple associations that we examined, our findings of an association between maternal use of OCs in early pregnancy and hypoplastic left heart syndrome and gastroschisis are compatible with chance, although we cannot rule out the possibility of real associations.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Use of Oral Contraceptives in Pregnancy and Major Structural Birth Defects in Offspring

et al. 2010

View full text Add to dashboard Cite

Previous reports of associations between OC use and specific types of anomalies were not corroborated. Given that associations were assessed for 32 types of birth defects, our findings of 2 increased associations between OC use and gastroschisis and hypoplastic left heart syndrome should be interpreted as hypotheses until they can be evaluated further. Overall, our findings are consistent with the majority of previous studies that found women who use OCs during early pregnancy have no increased risk for most types of major congenital malformations.

show abstract

Section: Discussionmentioning

confidence: 99%

“…9,10,12 Thus, we undertook the current study to assess the effect of maternal OC use among 9986 infants with major birth defects and 4000 infants without birth defects.…”

mentioning

confidence: 99%

Use of Oral Contraceptives in Pregnancy and Major Structural Birth Defects in Offspring

et al. 2010

View full text Add to dashboard Cite

show abstract

“…␤-AR stimulation plays a dual role in cardiac cell replication and differentiation, initially maintaining replication (41,57), and subsequently terminating replication and initiating differentiation (8,42); excessive stimulation elicits apoptosis (9). Accordingly, ␤-AR excitation in the immature organism, unrestrained by desensitization, may be responsible for the cardiac structural and physiological anomalies and the alterations in hepatic glucose metabolism that have been noted in neonates exposed to tocolytic ␤-AR agonists (5,25,36) …”

Section: Discussionmentioning

confidence: 99%

Are developing β-adrenoceptors able to desensitize? Acute and chronic effects of β-agonists in neonatal heart and liver

Auman

Seidler

Tate

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

During fetal and neonatal development, β-adrenergic receptors (β-ARs) appear to be resistant to desensitization by β-agonist drugs. To determine the mechanisms underlying the regulatory differences between adults and neonates, we administered isoproterenol, a mixed β1/β2-AR agonist, and terbutaline, a β2-selective agonist. Effects were examined in the ensuing 4 h after a single injection, or after the last of four daily injections. We prepared cell membranes from heart (predominantly β1-ARs) and liver (predominantly β2-ARs) and assessed signal transduction in the adenylyl cyclase (AC) pathway. In the first few hours after a single administration of isoproterenol to adult rats, cardiac β-ARs showed activation of G proteins (elevated AC response to forskolin) and desensitization of β-AR-mediated responses; after the fourth injection, heterologous desensitization emerged, characterized by a loss of signaling mediated either through β-ARs or glucagon receptors. Terbutaline evoked an increase in the forskolin response but no desensitization of receptor-mediated responses. When we gave the same treatments to neonatal rats, we observed cardiac G protein activation, but there was neither homologous nor heterologous desensitization of β-ARs or glucagon receptors. In the adult liver, isoproterenol and terbutaline both failed to evoke desensitization, regardless of whether the drugs were given once or for 4 days. In neonates, however, acute or chronic treatment elicited homologous desensitization of β-AR-mediated AC signaling, while sensitizing the response to glucagon. These results show that neonatal β-ARs are inherently capable of desensitization in some, but not all, cell types; cellular responses can be maintained through heterologous sensitization of signaling proteins downstream from the receptor. Differences from adult patterns of response are highly tissue selective and are likely to depend on ontogenetic differences in subtypes of β-ARs and AC.

show abstract

“…Hypertensive disorders and antihypertensive medication use in early pregnancy have both been suggested to directly affect fetal development through vascular disruption or other teratogenic mechanisms, and a number of studies have explored whether the prevalence of specific birth defects may be increased by hypertension or its treatment. Previous studies reported associations between early prenatal antihypertensive medication exposure and a number of specific birth defects, including congenital heart defects (CHDs), severe hypospadias, cleft lip with or without cleft palate, gastroschisis, and malformations of the central nervous system (CNS), but not birth defects overall . Hypospadias and CHDs have also been associated with the initiation of antihypertensive medication after the etiologically relevant time period for these defects, and with untreated maternal hypertension, but the authors were unable to distinguish among the different types of hypertensive disorders.…”

Section: Introductionmentioning

confidence: 99%

Maternal hypertensive disorders, antihypertensive medication use, and the risk of birth defects: a case–control study

Gelder

Bennekom

Louik

et al. 2014

BJOG

View full text Add to dashboard Cite

Objective To study previously identified associations between specific maternal hypertensive disorders and/or prenatal exposure to antihypertensive medication and birth defects.Design Case-control study.Setting Slone Birth Defects Study, 1998-2010.Population A total of 5568 cases with birth defects and 7253 liveborn infants without malformations as controls.Methods Adjusted odds ratios (aORs) for birth defects associated with prenatal exposure to maternal hypertensive disorders and/or antihypertensive medication were calculated using multivariable logistic regression analyses.Main outcome measures Specific birth defects previously linked to maternal hypertension or antihypertensive medication use during pregnancy.Results Non-pharmacologically managed chronic hypertension was associated with a three-fold risk of oesophageal atresia (95% CI 1.2-8.3), and pre-eclampsia superimposed on nonpharmacologically managed chronic hypertension was associated with ventricular septal defects (aOR 3.9, 95% CI 1.3-11.7) and atrial septal defects (aOR 6.5, 95% CI 1.8-23.7). For chronic hypertension that was pharmacologically treated early in pregnancy, increased risks were observed for first-degree hypospadias (aOR 2.9, 95% CI 1.1-7.4). Non-pharmacologically managed pre-eclampsia was related to second-/third-degree hypospadias and ventricular septal defects. Pharmacological treatment for gestational hypertension was associated with a number of congenital heart defects.Conclusions Our results confirm some, but not all, previously identified associations between pharmacologically treated and non-pharmacologically managed hypertensive disorders and specific birth defects. They support the hypothesis that physiological changes early in pregnancy that manifest in gestational hypertension and pre-eclampsia may play a role in the aetiology of major birth defects, including congenital heart defects and hypospadias.

show abstract

Serial examination of 20,248 newborn fetuses and infants: Correlations between drug exposure and major malformations

Cited by 11 publications

References 20 publications

Use of Oral Contraceptives in Pregnancy and Major Structural Birth Defects in Offspring

Use of Oral Contraceptives in Pregnancy and Major Structural Birth Defects in Offspring

Are developing β-adrenoceptors able to desensitize? Acute and chronic effects of β-agonists in neonatal heart and liver

Maternal hypertensive disorders, antihypertensive medication use, and the risk of birth defects: a case–control study

Contact Info

Product

Resources

About