Vasoactive exposures during pregnancy and risk of microtia

BACKGROUND

Little is known about the etiology of nonsyndromic microtia. This study investigated the hypothesis that microtia is caused by vascular disruption.

METHODS

The study analyzed data from the population‐based National Birth Defects Prevention Study (NBDPS) for deliveries between 1997 and 2005. Four hundred eleven nonsyndromic cases of microtia, with or without additional defects, were compared to 6560 nonmalformed infants with respect to maternal exposures to vasoactive medications and smoking during the periconceptional period and conditions that have previously been associated with vascular events (multiple gestation, maternal history of type 1, type 2, or gestational diabetes, and hypertension). Odds ratios (ORs) were estimated with multivariable models, controlling for the effects of race/ethnicity, education, periconceptional folic acid use, and study center.

RESULTS

Risk estimates for vasoactive medications and smoking were not meaningfully increased. Maternal type 1/2 diabetes was diagnosed before or during the index pregnancy in 4% and 1% of cases, respectively, compared to 1% and 0.05% of controls; the adjusted OR for these two groups combined was 7.2 (95% confidence interval [CI], 3.9–13.1). Gestational diabetes was observed for 9% of cases and 6% of controls; the OR was moderately elevated (OR, 1.4; 95% CI, 0.9–2.0). ORs were also increased for multiple gestations (OR, 2.5; 95% CI, 1.5–4.2) and pre‐existing hypertension (OR, 1.6; 95% CI, 1.0–2.5).

CONCLUSIONS

Because ORs were only elevated for diabetes and not for vasoactive exposures or other potential vascular events, findings suggest that some microtia occurrences may be part of the diabetic embryopathy rather than manifestations of vascular disruption. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.     

Demographic, reproductive, medical, and environmental factors in relation to gastroschisis.

To identify risk factors for gastroschisis other than drug use in pregnancy, an analysis of data collected in a case-control surveillance program of birth defects (1976-1990) was conducted. Drug use is considered in Werler et al., Teratology, 45:361-367, 1992. Maternal demographic, reproductive, and medical factors, and first trimester environmental exposures, were compared between 76 gastroschisis cases and 2,581 malformed controls. A strong inverse association was found for maternal age: relative to women 30 years or older, relative risks for 25-29, 20-24, and less than 20-year-old women were 1.7, 5.4, and 16, respectively. Multivariate relative risks (and 95% confidence intervals) for alcohol use were as follows: for 1-5 drinks per week, 1.6 (0.7-3.4); for greater than or equal to 6 drinks per week, 2.5 (0.9-6.8); for a maximum of 1-4 drinks at any one time, 0.8 (0.4-1.6); and for a maximum of greater than or equal to 5 drinks, 2.8 (1.2-6.5). With the effect of age taken into account, no associations were identified for cigarette smoking, consumption of caffeinated or decaffeinated coffee, unplanned pregnancy, 12 or less years of education, or a parity of two or more. Other medical and reproductive factors, including weight gain, vaginal bleeding, nausea or vomiting, influenza, "other" infection, and history of spontaneous abortion or elective abortion did not increase the risk.     

First trimester maternal medication use in relation to gastroschisis.

In a case-control surveillance program, first trimester medication use was studied in relation to gastroschisis. There were 76 cases of gastroschisis which were compared with 2,142 controls with other major malformations. For pseudoephedrine use, we found a significantly elevated relative risk of 3.2 (95% confidence interval, 1.3-7.7), with adjustment for confounding. Multivariate relative risks for analgesic/antipyretics and another decongestant were as follows: salicylates, 1.6 (0.9-2.7); acetaminophen, 1.7 (1.0-2.9); ibuprofen, 1.3 (0.4-3.7); and phenylpropanolamine, 1.5 (0.4-5.4). No increases in risk were identified for use of antihistamines, antibiotics, oral contraceptives, or spermicides. Because salicylates, pseudoephedrine, and phenylpropanolamine are vasoactive, the elevated risks for these drugs support the hypothesis of vascular disruption in the etiology of gastroschisis. We therefore examined maternal use of vasoactive medications in relation to a second case group of 416 infants with hetereogeneous defects suspected to have a vascular etiology. Relative risks for salicylates, ibuprofen, pseudoephedrine, phenylpropanolamine, and other decongestants approximated unity. These positive associations must be considered tentative. They have not been reported previously and should be confirmed independently. Also, acetaminophen, which may be taken for the same indications as salicylates and decongestants, but is not thought to be vasoactive, was associated with gastroschisis, suggesting that identified associations may be due to an underlying maternal illness.     

Associations between periconceptional alcohol consumption and craniosynostosis, omphalocele, and gastroschisis

BACKGROUND: Alcohol consumption during pregnancy is known to be associated with certain birth defects, but the risk of other birth defects is less certain. The authors examined associations between maternal alcohol consumption during pregnancy and craniosynostosis, omphalocele, and gastroschisis among participants in the National Birth Defects Prevention Study, a large, multicenter case–control study. METHODS: A total of 6622 control infants and 1768 infants with birth defects delivered from 1997–2005 were included in the present analysis. Maternal alcohol consumption was assessed as any periconceptional consumption (1 month prepregnancy through the third pregnancy month), and by quantity‐frequency, duration, and beverage type. Alcohol consumption throughout pregnancy was explored for craniosynostosis since the period of development may extend beyond the first trimester. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression analysis. OR were adjusted for age, race/ethnicity, and state of residence at time of infant's birth. Gastroschisis OR were also adjusted for periconceptional smoking. RESULTS: Periconceptional alcohol consumption and craniosynostosis showed little evidence of an association (OR = 0.92; CI: 0.78–1.08), but alcohol consumption in the second (OR = 0.65; CI: 0.47–0.92) and third trimesters (OR = 0.68; CI: 0.49–0.95) was inversely associated with craniosynostosis. Periconceptional alcohol consumption was associated with omphalocele (OR = 1.50; CI: 1.15–1.96) and gastroschisis (OR = 1.40; CI: 1.17–1.67). CONCLUSIONS: Results suggest that maternal periconceptional alcohol consumption is associated with omphalocele and gastroschisis, and second and third trimester alcohol consumption are inversely associated with craniosynostosis. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.     

影响剖宫产术后并发产褥感染的相关危险因素分析

目的:探讨剖宫产术后产褥感染的相关危险因素,为临床制定感控措施提供参考。方法:回顾性分析我院接受剖宫产术的1760例孕妇的临床资料,采用单因素卡方检验及多因素Logistic回归方法对剖宫产术后发生产褥感染的相关危险因素进行统计学分析。结果:1760例接受剖宫产手术的孕妇,术后发生产褥感染的有68例,发生率为3.86%;发生产褥感染最常见的部位是急性子宫内膜炎、子宫肌炎,其构成比占57.4%;经过单因素卡方检验及多因素Logistic回归分析,最终筛选出手术时间(OR=1.351)、血红蛋白(OR=1.759)、胎膜早破(OR=2.247)、孕期生殖道感染反复发作(OR=2.047)、妊娠糖尿病(OR=1.473)、前置胎盘反复阴道出血(OR=1.584)与宫产术后发生产褥感染呈正相关(P0.05)。结论:手术时间、血红蛋白、胎膜早破、孕期生殖道感染反复发作、妊娠糖尿病、前置胎盘反复阴道出血是剖宫产后发生产褥感染的高危因素,临床应针对这些高危因素制定干预措施以降低感染的发生率。     

First trimester exposure to paroxetine and risk of cardiac malformations in infants: the importance of dosage

BACKGROUND: Conflicting findings with regard to the teratogenic risks of first trimester use of paroxetine have prompted the FDA, Health Canada, and the manufacturer of the drug to issue warnings against its use during pregnancy. Given that untreated depression during pregnancy can lead to deleterious effect on the mother and her unborn fetus, data on the relationship between the dose and the range of malformations is warranted. This study attempts to quantify the association between first trimester exposure to paroxetine and congenital cardiac malformations, adjusting for possible confounders, and to quantify the dose-response relationship between paroxetine use and cardiac defects. METHODS: The Medication and Pregnancy registry was used. This population-based registry was built by linking three administrative databases (RAMQ, Med-Echo, and ISQ), and includes all pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of entry in the registry is the date of the first day of the last menstrual period. To be eligible for this study, women had to: 1) be 15-45 years of age at entry; 2) be covered by the RAMQ drug plan >or=12 months before and during pregnancy; 3) be using only one type of antidepressant during the first trimester; and 4) have a live birth. Two nested case-control studies were carried out comparing the prevalence of paroxetine use in the first trimester of pregnancy to the prevalence of other antidepressant exposures during the same time period. Cases were defined as: 1) any major malformations; or 2) any cardiac malformations diagnosed in the first year of life; controls were defined as no major or minor malformations. Multivariate logistic regression techniques were used to analyze data. RESULTS: Among the 1,403 women meeting inclusion criteria, 101 infants with major congenital malformations were identified; 24 had cardiac malformations. Adjusting for possible confounders, the use of paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 0.49-3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28-2.84) during the first trimester of pregnancy did not increase the risk of congenital cardiac malformations compared with the use of non-SSRI antidepressants. When considering the dose, however, a dose-response relationship was observed, thus women exposed to >25 mg/day of paroxetine during the first trimester of pregnancy were at increased risk of having an infant with major congenital malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42). CONCLUSIONS: Gestational exposure to paroxetine is associated with major congenital malformations and major cardiac malformations for only first trimester exposure above 25 mg/day.     

Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy

Objective:

The prevalence of overweight and obesity among women of reproductive age is increasing. We aimed to determine risk factors and maternal, fetal and childhood consequences of maternal obesity and excessive gestational weight gain.

Design and Methods:

The study was embedded in a population‐based prospective cohort study among 6959 mothers and their children. The study was based in Rotterdam, The Netherlands (2001–2005).

Results:

Maternal lower educational level, lower household income, multiparity, and FTO risk allel were associated with an increased risk of maternal obesity, whereas maternal European ethnicity, nulliparity, higher total energy intake, and smoking during pregnancy were associated with an increased risk of excessive gestational weight gain (all p‐values <0.05). As compared to normal weight, maternal obesity was associated with increased risks of gestational hypertension (OR 6.31 (95% CI 4.30, 9.26)), preeclampsia (OR (3.61, (95% CI 2.04, 6.39)), gestational diabetes (OR 6.28 (95%CI 3.01, 13.06)), caesarean delivery (OR 1.91 (95% CI 1.46, 2.50)), delivering large size for gestational age infants (OR 2.97 (95% CI 2.16, 4.08)), and childhood obesity (OR 5.02 (95% CI:2.97, 8.45)). Weaker associations of excessive gestational weight gain with maternal, fetal and childhood outcomes were observed, with the strongest effects for first trimester weight gain.

Conclusions:

Our study shows that maternal obesity and excessive weight gain during pregnancy are associated with socio‐demographic, lifestyle, and genetic factors and with increased risks of adverse maternal, fetal and childhood outcomes. As compared to prepregnancy overweight and obesity, excessive gestational weight gain has a limited influence on adverse pregnancy outcomes.     

Teratogen update: pseudoephedrine

Pseudoephedrine is contained in decongestants such as the Sudafed line of products. It is an alpha-adrenergic receptor agonist, which causes blood vessel constriction, including the therapeutic effect of reducing airflow resistance in the nasal cavity. Pseudoephedrine is one of the most commonly used medications in pregnancy, with an estimated 25% of women exposed. It has been demonstrated that alpha-adrenergic receptor agonists slow uterine blood flow, but their effects have not been studied in relation to most reproductive outcomes in animals or humans. Two analyses of health maintenance organization pharmacy data identified 9 malformed infants among 902 first-trimester pseudoephedrine exposures, suggesting no association with birth defects overall; however, studies of such data sets often lack sufficient power to identify risks for specific birth defects. The related compounds, epinephrine, ephedrine, and phenylephrine, have been associated with hemorrhages and cardiovascular and limb malformations in animal models. Risk of ventricular septal defects was associated with decongestant use in pregnant women in 1 recent study. The vasoconstrictive effects of these drugs raise the hypothesis that their use in early pregnancy might increase the risk of vascular disruption defects. Case-control studies, which often do have power to identify risks related to specific birth defects, have explored this hypothesis. Decongestant use in the first trimester has been associated with small increases in risks of 3 defects thought to arise, at least in some instances, from vascular disruption-gastroschisis, small intestinal atresia, and hemifacial microsomia. These findings are somewhat consistent in terms of magnitude of effect and suggest that risks are even greater among women also exposed to the vasoconstrictive effects of cigarette smoking. There are, however, limitations to these studies, including the possibilities of inaccurate recall of exposures and confounding by indication. In addition, the majority of decongestant use is in oral form and the question of whether intranasal formulations carry risk has not been adequately addressed.     

Maternal factors in congenital limb-reduction defects

Various maternal characteristics were examined in case-control studies of limb-reduction defects among live births in Upstate New York (i.e., New York State exclusive of New York City). In a study using birth records of 305 cases and 915 controls born in 1970-81, mean birth weight and gestation length were significantly lower in cases than in controls, and certain pregnancy complications (i.e., abnormal vaginal bleeding and diabetes mellitus) were reported more often in cases than in controls. Several subgroups of defects (i.e., isolated defects vs. multiple, long-bone defects vs. other) were also compared with their respective controls. The subgroup with multiple (including nonskeletal) defects had the lowest mean birth weight and length of gestation. In an interview study of 108 cases and 108 controls born in 1968-74, a history of maternal use of thyroid medication was a significant risk factor; possible explanations for this association are discussed.     

Obstetric outcome in donor oocyte pregnancies: a matched-pair analysis

ABSTRACT: BACKGROUND: To investigate the obstetrical and perinatal impact of oocyte donation, a cohort of women who conceived after OD was compared with a matched control group of women who became pregnant through in vitro fertilisation with autologous oocytes (AO). METHODS: A matched-pair analysis has been performed at the Centre for Reproductive Medicine of the UZ Brussel, Dutch speaking Free University of Brussel. A total of 410 pregnancies resulted in birth beyond 20 weeks of gestation occurring over a period of 10 years, including 205 oocyte donation pregnancies and 205 ICSI pregnancies with autologous oocytes (AO). Patients in the OD group were matched on a one-to-one basis with the AO group in terms of age, ethnicity, parity and plurality. Matched groups were compared using paired t-tests for continuous variables and McNemar test for categorical variables. A conditional logistic regression analyses was performed adjusting for paternal age, age of the oocyte donor, number of embryos transferred, and singleton/twin pregnancy. RESULTS: Oocyte donation was associated with an increased risk of pregnancy induced hypertension (PIH) (matched OR: 1.502 CI: 1.024-2.204), and first trimester bleeding (matched OR: 1.493 CI: 1.036-2.15). No differences were observed between the two matched groups with regard to gestational age, mean birth weight and length, head circumference and Apgar scores. CONCLUSIONS: Oocyte donation is associated with an increased risk for PIH and first trimester bleeding independent of the recipients? age, parity and plurality, and independent of the age of the donor or the partner. However, oocyte donation has no impact on the overall perinatal outcome.