Pregnancy outcome after gestational exposure to mebendazole: a prospective controlled cohort study

OBJECTIVE: Mebendazole is an anthelmintic that is commonly needed in women of reproductive age. Its use in pregnancy is a reason for concern for women and their health care providers. The purpose of this study was to examine the fetal safety of mebendazole. STUDY DESIGN: The Israeli Teratogen Information Service prospectively collected and followed 192 pregnancies exposed to mebendazole in pregnancy, 71.5% of whom had first-trimester exposure. Pregnancy outcome was compared with that of a matched control group, who were counseled for nonteratogenic exposure. RESULTS: There was no increase in the rate of major malformations between the groups (5/150 pregnancies [3.3%; mebendazole] vs 3/175 pregnancies [1.7%; nonteratogenic control subjects]; P =.478). There was a higher rate of elective terminations of pregnancy in the exposed group compared with the control group (22/192 pregnancies [11.5%; mebendazole] vs 3/192 pregnancies [1.6% [nonteratogenic control subjects]; P =.000). CONCLUSION: This study suggests that mebendazole does not represent a major teratogenic risk in humans when it is used in the doses that are used commonly for pinworm (Enterobius vermicularis) infestation.     

Neonatal outcome after exposure to indomethacin in utero: a retrospective case cohort study

OBJECTIVE: This study was undertaken to determine the clinical outcome for neonates who were exposed to indomethacin during gestation. STUDY DESIGN: We identified 124 infants with in utero exposure to indomethacin and matched them to 124 infants whose mothers did not receive indomethacin. The two groups were matched for gestational age at birth, sex, and exposure to antenatal betamethasone. Sixty-two of the indomethacin-exposed infants were born within 48 hours of last exposure. These infants were also compared with their matched controls. RESULTS: There were no significant differences between the indomethacin-exposed infants and control infants in birth weight, Apgar scores, frequency of cesarean section deliveries, and multiple gestation. The incidence of respiratory distress syndrome, need for surfactant treatment, patent ductus arteriosus, necrotizing enterocolitis, and intraventricular hemorrhage was similar between the indomethacin-exposed group and the control group. Indomethacin-exposed infants who were born within 48 hours of last exposure had similar incidence of respiratory distress syndrome but greater need for surfactant treatment (P=.02) compared with controls. All other complication rates were similar. CONCLUSION: Indomethacin exposure in our study was not associated with increased neonatal complications for infants delivered within or beyond 48 hours of last exposure.     

Pregnancy outcome following first-trimester exposure to zopiclone: a prospective controlled cohort study.

BACKGROUND & AIM: Zopiclone, a cyclopyrrolone derivative, is a short-acting hypnotic. To date, no published data exist regarding human pregnancy experience with zopiclone. The purpose of this study was to compare pregnancy outcome following first-trimester exposure to zopiclone with that of a matched control group of women, who were counseled for nonteratogenic exposure. METHODS: The Motherisk Program, the Toronto Teratogen Information Service, prospectively collected and followed up 40 women exposed to zopiclone during pregnancy. Pregnancy outcome was compared with that of a matched control group of women, who were counseled for nonteratogenic exposure. RESULTS: There was no increase in the rate of major malformations (0 of 31 [0%] for zopiclone vs. 1 of 37 [2.7%] for nonteratogenic controls; p = 1). CONCLUSIONS: Our study, which is the first cohort on zopiclone use during embryogenesis, albeit small, suggests that zopiclone does not appear to be a major human teratogen. Larger studies are needed to establish its safety during pregnancy.     

Pregnancy outcome after gestational exposure to the new macrolides: a prospective multi-center observational study

Objectives

To determine whether the use of the new macrolides (azithromycin, clarithromycin, roxithromycin) during the first trimester of pregnancy is associated with an increased risk of major malformations.

Study design

In a prospective multi-center study, pregnancy outcome was compared between pregnant women exposed to one of the new macrolides during the first trimester of pregnancy and two comparison groups one exposed to other antibiotics and the other to other non-teratogenic medications. All women enrolled in the study called one of the three participating teratogen information services (TIS). Group 1 macrolides (n = 161), group 2 other antibiotics (n = 213) and group 3 non-teratogens (n = 740).

Results

A total of 161 women exposed to the new macrolides (118 were exposed in the first trimester of pregnancy) and 953 from a comparison groups were followed up. The rate of major malformations in the study group was 4.1% compared to 2.1% in the other antibiotics exposed group (OR = 1.41, 95% CI 0.47–4.23) and 3.0% in the non-teratogens exposed group. The rate of elective terminations of pregnancy was significantly higher in the exposed group in compare to both comparison groups.

Conclusion

Our study, although relatively small sized, suggests that the use of the new macrolides during the first trimester of pregnancy does not represent an increased risk for congenital malformations strong enough for an induced abortion after such an exposure. Elective terminations of pregnancy because of early exposure to these medications should be reconsidered.     

Pregnancy course and outcome after intracytoplasmic sperm injection: a controlled, prospective cohort study

OBJECTIVE: To determine pregnancy course and major malformation rate after intracytoplasmic sperm injection (ICSI). DESIGN: Prospective, controlled, multicenter, nationwide German cohort study. SETTING: Tertiary infertility centers in Germany. PATIENT(S): Three thousand three hundred seventy-two children and fetuses and 8,016 children and fetuses after the 16th week of gestation in pregnancies after ICSI and natural conception, respectively. INTERVENTION(S): Standardized prospective follow-up. MAIN OUTCOME MEASURE(S): Major malformation rate. RESULT(S): The major malformation rate was 8.7% (295/3,372) for the ICSI cohort and 6.1% (488/8,016) for the population-based control cohort (relative risk, 1.44 [1.25-1.65]). After adjustment for risk factors, the risk declined (adjusted odds ratio, 1.24 [95% CI, 1.02-1.50]). Regarding singletons, there was a significant difference for birth weight and gestational age, with a higher number of preterm and low birth weight children in pregnancies achieved after ICSI. CONCLUSION(S): Children who are born after intracytoplasmic sperm injection have an increased risk of a major congenital malformation compared with those born after spontaneous conception. This risk is mainly due to paternal and maternal risk factors, which are more prevalent in couples who use ICSI for reproduction. An infertility-linked risk is highly probable for the observed findings. A technique-related risk, however, cannot be ruled out.     

Neonatal outcome following pregnancy exposure to antidepressants: a prospective controlled cohort study

Objective  To determine the incidence of early adverse effects associated with antidepressant drug use during pregnancy.
Design  Prospective, controlled cohort study.
Setting  A Drug and Health Information Centre in Milan, Italy.
Population  A total of 200 neonates exposed to antidepressants in utero and 1200 controls.
Methods  Women who took antidepressants during pregnancy and delivered liveborn children between 1995 and 2003 were selected. Each case was matched for maternal age and gravidity to six randomly selected controls (not exposed to teratogenic drugs or drugs known to cause neonatal side effects). Odds ratio was estimated for attributable risks.
Main outcome measures  Neonatal adverse events and Special Care Unit admission rate, assessed through an interview with the mothers.
Results  Of the 200 neonates exposed to antidepressants in utero , 14 had adverse events and 3 required Special Care Unit admission. Jaundice ( n = 5), agitation ( n = 3) and respiratory distress ( n = 2) were the most common symptoms. In the control group, 50 newboms had side effects and no statistically significant differences in the prevalence rate compared to the exposed group were found, even after stratification for drugs and pregnancy period of exposure. Only the prematurity rate was significantly higher in exposed compared to non-exposed newborns (OR = 2.31; 95% CI 1.14–4.63).
Conclusions  These results do not support an association between antidepressant exposure and unsafe fetal and neonatal outcomes in newborns. However, a collaborative international multicentre epidemiological monitoring of the use of psychotropic drugs during pregnancy is needed in order to guarantee pregnant women and their children safe and effective treatments, both at brief and long time from exposure.     

Cancer during pregnancy: perinatal outcome after in utero exposure to chemotherapy

Objectives

To study the outcome of pregnancies complicated by malignant disease, in particular neonatal morbidity and mortality after in utero exposure to chemotherapy.

Methods

This prospective study included 118 patients diagnosed with malignant disease for the first time during pregnancy over an 8-year period (March 2003?CMarch 2011). Outcome of neonates born to mothers who received chemotherapy during pregnancy was studied and compared with a control group.

Results

The commonest cancer type diagnosed during pregnancy (56/118?=?47.45?%) was breast carcinoma followed by lymphoma/leukemia (32?=?27.12?%). Gynecological tumors (all ovarian) represented 10.16?%, soft tissue tumors 5.08?%, colorectal 4.23?%, thyroid 2.54?% and others 3.38?%. Sixty-one (51.64?%) women received chemotherapy (average 3?±?2 cycles) during the second and third trimesters. The incidence of neonatal survival, preterm birth, small for gestational age and congenital malformations was not significantly different between women who received chemotherapy during pregnancy and the control group. Five (4.23?%) women with advanced disease died during or shortly after termination of pregnancy.

Conclusion

In utero exposure to chemotherapy during the second and third trimesters of pregnancy carries minimal morbidity to the unborn fetus.     

Pregnancy outcome among obese women: a prospective study

We investigated pregnancy outcome among obese women using a prospective cohort study comparing consecutive deliveries of obese and nonobese patients. Stratified analysis, using the Mantel-Haenszel technique, was done to assess the association between obesity and the risk for cesarean delivery (CD) while controlling for confounding variables. Complete data were abstracted for 376 women, of whom 21% ( N = 79) were obese. CD rate was significantly higher among obese women (32.9% versus 18.9%; P = 0.006). Maternal obesity was associated with multiparity (odds ratio [OR] 2.97, 95% confidence interval [CI] 1.27 to 6.97; P = 0.012), fertility treatments (OR 11.3, 95% CI 2.84 to 44.89; P = 0.001), insulin-treated gestational diabetes (OR 24.55, 95% CI 2.28 to 264.08; P = 0.008), and hydramnios (OR 20.46, 95% CI 2.17 to 192.89; P = 0.008). When controlling for possible confounders, the association between maternal obesity and CD remained significant (weighted OR 2.2, 95% CI 1.2 to 4.1; P = 0.018). No significant differences were noted between the groups regarding neonatal complications. Both first and second stages of labor were longer in obese women. Obesity is a risk factor for developing gestational hypertension, insulin-treated gestational diabetes, and hydramnios. Moreover, maternal obesity is an independent risk factor for CD. Additional independent risk factors for CD were fertility treatments, insulin-treated gestational diabetes, and hydramnios. However, neonatal outcome of obese women is comparable to women with normal prepregnancy body mass index.     

Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study

OBJECTIVE: Bupropion was developed for the treatment of depression, but subsequently was found to be effective for smoking cessation. To date, there are no prospective comparative studies examining its safety in pregnancy. The primary objective was to determine whether bupropion increases the risks for major malformations above baseline. The secondary objective was to examine the rates of live births, stillbirths, spontaneous and therapeutic abortions, mean birth weight, and gestational age at birth. STUDY DESIGN: Women who were pregnant or planning a pregnancy and taking bupropion were enrolled in the study. Follow-up of pregnancy outcome was carried out between 4 months and 1 year after delivery. Three comparisons were carried out: 1) women exposed to bupropion vs a nonteratogen group; 2) those taking for depression vs other antidepressants, vs a nonteratogen group; 3) spontaneous abortions were compared between those taking for depression, vs another antidepressant group vs a nonteratogen group. RESULTS: We completed follow-up on 136 women exposed to bupropion during the first trimester of pregnancy. There were (105) live births, no major malformations, the mean birth weight was (3450g), the mean gestational age at delivery was (40 weeks), the number of spontaneous abortions was 20, there were 10 therapeutic abortions, there was 1 stillbirth, and 1 neonatal death. There were no statistically significant differences between any of the end points we examined between the exposed and comparison groups, with the exception of significantly more spontaneous abortions in the bupropion group (P = .009). CONCLUSION: These results suggest that bupropion does not increase the rates of major malformation above baseline. The higher rates of spontaneous abortions are similar to other studies examining the safety of antidepressants during pregnancy.     

Pregnancy outcome after exposure to the probiotic Lactobacillus in early pregnancy

The present study prospectively assessed pregnancy outcome of women taking probiotics during the periconceptional period. A group of 104 women who had taken Lactobacillus in early pregnancy and 200 age- and parity-matched control pregnant women exposed to non-teratogenic agents were also recruited into the study and followed-up prospectively. Median gestational age of women exposed to Lactobacillus was 5.2 (range: 1.9-17.6) weeks. Exposure was at a mean dose of 510 mg/day for a median of 4.0 days (range: 1-90 days). In the exposed group, pregnancy outcomes included 96 live births and eight spontaneous abortions versus 187 live births and 21 spontaneous abortions in the non-exposed group. There was no statistical difference in adverse pregnancy outcomes, including the number of spontaneous abortions, pre-term births as well as a low birth weight between the two groups (p > 0.05). In the exposed group, there were two (2.1%) major congenital malformations in comparison with five (2.7%) in the comparison group (p = 0.7). In conclusion, no association was identified between ingestion of Lactobacillus in early pregnancy for a limited period of time and adverse pregnancy outcomes. However, rare pregnancy outcomes may have been missed due to the limited sample size included in the study.     

Mode of childbirth and neonatal outcome after external cephalic version: A prospective cohort study

Objectiveto assess the mode of childbirth and adverse neonatal outcomes in women with a breech presentation with or without an external cephalic version attempt, and to compare the mode of childbirth among women with successful ECV to women with a spontaneous cephalic presentation.Designprospective matched cohort study.Setting25 clusters (hospitals and its referring midwifery practices) in the Netherlands. Data of the Netherlands perinatal registry for the matched cohort.Participantssingleton pregnancies from January 2011 to August 2012 with a fetus in breech presentation and a childbirth from 36 weeks gestation onwards. Spontaneous cephalic presentations (selected from national registry 2009 and 2010) were matched in a 2:1 ratio to cephalic presentations after a successful version attempt. Matching criteria were maternal age, parity, gestational age at childbirth and fetal gender. Main outcomes were mode of childbirth and neonatal outcomes.Measurements and findingsof 1613 women eligible for external cephalic version, 1169 (72.5%) received an ECV attempt. The overall caesarean childbirth rate was significantly lower compared to women who did not receive a version attempt (57% versus 87%; RR 0.66 (0.62–0.70)). Women with a cephalic presentation after ECV compared to women with a spontaneous cephalic presentation had a decreased risk for instrumental vaginal childbirth (RR 0.52 (95% CI 0.29–0.94)) and an increased risk of overall caesarean childbirth (RR 1.7 (95%CI 1.2–2.5)).Key conclusionswomen who had a successful ECV are at increased risk for a caesarean childbirth but overall, ECV is an important tool to reduce the caesarean rate.Implication for practiceECV is an important tool to reduce the caesarean section rates.     

Anal incontinence after vaginal delivery: a five-year prospective cohort study

OBJECTIVE: The long-term prevalence of anal incontinence after vaginal delivery is unknown. The aim of the present study was to evaluate the prevalence of anal incontinence in primiparous women 5 years after their first delivery and to evaluate the influence of subsequent childbirth. METHODS: A total of 349 nulliparous women were prospectively followed up with questionnaires before pregnancy, at 5 and 9 months, and 5 years after delivery. A total of 242 women completed all questionnaires. Women with sphincter tear at their first delivery were compared with women without such injury. Risk factors for development of anal incontinence were also analyzed. RESULTS: Anal incontinence increased significantly during the study period. Among women with sphincter tears, 44% reported anal incontinence at 9 months and 53% at 5 years (P = .002). Twenty-five percent of women without a sphincter tear reported anal incontinence at 9 months and 32% had symptoms at 5 years (P < .001). Risk factors for anal incontinence at 5 years were age (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.0-1.2), sphincter tear (OR 2.3; 95% CI 1.1-5.0), and subsequent childbirth (OR 2.4; 95% CI 1.1-5.6). As a predictor of anal incontinence at 5 years after the first delivery, anal incontinence at both 5 months (OR 3.8; 95% CI 2.0-7.3) and 9 months (OR 4.3; 95% CI 2.2-8.2) was identified. Among women with symptoms, the majority had infrequent incontinence to flatus, whereas fecal incontinence was rare. CONCLUSION: Anal incontinence among primiparous women increases over time and is affected by further childbirth. Anal incontinence at 9 months postpartum is an important predictor of persisting symptoms.     

Pregnancy outcome following first trimester exposure to chloroquine

Although the use of chloroquine (C) and hydroxychloroquine (HC) in the treatment of malaria prophylaxis during pregnancy is probably safe, the use of much higher doses for treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis during pregnancy has been controversial. We analyzed the cases of 24 pregnant women with a total of 27 pregnancies who had taken these drugs during their first trimester of pregnancy. C and HC were given in 11 patients with SLE, three with rheumatoid arthritis, and four for malaria prophylaxis. Most of these women had already been on antimalarial drugs for 1 to 172 months prior to pregnancy (mean, 32.2 months). Of the 27 pregnancies, 14 resulted in normal full-term deliveries, six were aborted due to severe disease activity or social conditions, three were stillbirths, and four pregnancies resulted in spontaneous abortions. No congenital abnormalities were detected in the 14 live births at ages between 9 months and 19 years (mean, 5.3 years). All these children are physically and developmentally normal with no clinical evidence of eye or hearing defects. The seven pregnancies that were associated with fetal loss occurred particularly in patients who had active SLE, although stillbirth and spontaneous abortion occurred also in patients with rheumatoid arthritis and in two of the three patients who had been treated prophylactically for malaria. Although of the 215 reported pregnancies with C and HC exposure, including our study, only seven (3.3%) had congenital abnormalities, the risk associated with antimalarials may be cumulative and further studies are needed to elucidate the safety of this drug later in pregnancy.     

Prolonged neonatal complications after in utero exposure to fluoxetine

This article presents the case of a female newborn with irritability, increased tonus, jitteriness, and eating difficulties who was referred to our institution. Her mother had been taking fluoxetine (20 mg daily) during the second and third trimesters of her pregnancy. The infant's signs began on the first day after birth and persisted for 6 weeks. Extensive investigations excluded infective, genetic, and metabolic causes, and a provisional diagnosis of fluoxetine withdrawal was made. There have been few reports of neonatal complications following maternal fluoxetine hydrochloride treatment. According to these, signs occurred within a few days after birth and lasted up to 4 weeks. To our knowledge, our patient demonstrated the longest duration of signs reported to date. We recommend that physicians be aware of these complications in newborns after fetal exposure in utero to selective serotonin reuptake inhibitors. These neonates should be followed-up closely for adverse signs during the first days of life so that signs can be recognized and treated if necessary.