[Risk assessment of drugs during breastfeeding]. / Évaluation des risques liés aux médicaments pendant l'allaitement.

Medication intake during the postpartum period is common with discontinuation of breastfeeding sometimes unnecessarily recommended for fear of adverse effects in the breastfed infant, while exposure through human milk is generally low. The assessment of risks associated with medication intake during breastfeeding is based, among other things, on the little clinical evidence available in specialized sources of information, and on pharmacokinetic principles. A decision-making support is presented to facilitate communication with mothers, foster medication adherence and prevent unnecessary interruption of breastfeeding.

La prise de médicaments pendant la période postnatale est courante et associée à un arrêt de l'allaitement parfois recommandé à tort par crainte d'effets indésirables chez l'enfant allaité, alors que l'exposition à travers le lait maternel est généralement faible. L'évaluation des risques d'utilisation de médicaments pendant l'allaitement repose, entre autres, sur le peu de preuves cliniques disponibles, documentées dans des sources d'information spécialisées, et sur les principes pharmacocinétiques. Un algorithme d'aide à la décision est proposé pour faciliter la communication avec les mères, renforcer l'adhésion thérapeutique et éviter une interruption inutile de l'allaitement.

Infant exposure to Fluvoxamine through placenta and human milk: a case series - A contribution from the ConcePTION project.

Introduction: Fluvoxamine is widely used to treat depression during pregnancy and lactation. However, limited data are available on its transfer to the fetus or in human milk. This case series provides additional information on the infant exposure to fluvoxamine during pregnancy and lactation. Case presentation: Two women, aged 38 and 34 years, diagnosed with depression were treated with 50 mg fluvoxamine during pregnancy and lactation. At delivery a paired maternal and cord blood sample was collected for each woman. The first mother exclusively breastfed her child for 4 months and gave one foremilk and one hindmilk sample at 2 days and 4 weeks post-partum, whereas the second mother did not breastfeed. Results: The cord to plasma concentration ratios were 0.62 and 0.48, respectively. At 2 weeks post-partum, relative infant doses (RID) were 0.47 and 0.57% based on fluvoxamine concentrations in foremilk and hindmilk, respectively. At 4 weeks post-partum, the RIDs were 0.35 and 0.90%, respectively. The child from the first mother was born healthy and showed a normal development at the 6th, 18th and 36th month follow-ups. One of the twins from the second woman was hospitalized for hypoglycemia that was attributed to gestational diabetes and low birth weight. The second one was born healthy. Conclusion: These results suggest a minimal exposure to fluvoxamine during lactation which is in accordance with previously published data. Larger clinical and pharmacokinetic studies assessing the long-term safety of this drug during lactation and the variability of its exposure through breastmilk are warranted.

Transfer of Mexiletine into Breast Milk: A Case Report.

Background: Mexiletine is a class 1B antiarrhythmic agent, used to treat ventricular arrhythmias, and noncardiac-related problems such as myotonia. Limited safety data are available on the transfer of this drug into breast milk. Case Report: We report the case of a woman diagnosed with myotonia congenita who breastfed two children after two consecutive pregnancies. During the breastfeeding of the first and the second infant, she collected, respectively, five and seven samples at 0, 2, 4, 6, and 8 hours and 0, 1, 2, 3, 4, 6, and 8 hours after taking 200 mg of mexiletine thrice daily for seven doses. One week after the collection, samples were analyzed with a validated liquid chromatography tandem mass spectrometry method. No side effect was observed in either child according to the mother. Results: Using the mean milk concentrations, it is estimated that an exclusively breastfed infant would receive a maximum of 5.14% of the initial pediatric mexiletine dosage. We calculated a maximum of 2.67% for the first infant in our case, considering a nonexclusive breastfeeding. Maximal concentrations were observed 1-2 hours after the dose of mexiletine. Results seem to be in accordance with the two cases previously published. Conclusions: Mexiletine transfers into breast milk in low levels. However, results are obtained from only one woman. Therefore, caution should be used when mexiletine is prescribed to breastfeeding women. More cases are needed to evaluate the interindividual variability and to guide women regarding breastfeeding with mexiletine.

Maternal drugs and breastfeeding: Risk assessment from pharmacokinetics to safety evidence - A contribution from the ConcePTION project.

Human milk is the most appropriate form of nutrition for infants while taking medication during the postpartum period is common. Discontinuation of breastfeeding is sometimes wrongly recommended for fear of adverse effects in the breastfed infant whereas only a few drugs are strictly contraindicated while breastfeeding. Most drugs are transferred from the mother's blood to the milk, but the breastfed infant usually ingests a small drug amount through human milk. As population-based evidence is still scarce on safety of drugs during breastfeeding, risk assessment relies on the little clinical evidence available and on pharmacokinetic principles, as well as on specialized sources of information that are essential for clinical decision-making. Risk assessment should not only be based on the drug's potential risk for the breastfed infant but should always take into account the benefits associated to breastfeeding, the risks of untreated maternal disease and the maternal willingness to breastfeed. Identifying situations with potential for drug accumulation in the breastfed infant is decisive while assessing the risk. Health care providers should always assume that mothers will be concerned and use risk communication as a key to ensure medication adherence and prevent unnecessary interruption of breastfeeding. When a mother still expresses concerns, decision support algorithms may facilitate communication and some strategies can be offered to minimize the drug exposure in the breastfed infant even when clinically not justified.

Relationship between raltegravir trough plasma concentration and virologic response and the impact of therapeutic drug monitoring during pregnancy.

BACKGROUND: Limited data is available on raltegravir (RAL) pharmacokinetics during pregnancy and the value of therapeutic drug monitoring (TDM) in pregnancy is unknown. This study aims to describe RAL trough plasma concentrations (Ctrough) during pregnancy and review the impact of RAL TDM on outcomes. METHODS: Women from the prospective mother-infant HIV cohort of Mother and Children's Infectious Diseases Center who received RAL during their pregnancy between 2011-2020 were included. TDM reports were reviewed and Ctrough values estimated when possible, using historical RAL half-lives. RESULTS: We included 76 pregnant women of which 47 underwent TDM. We observed a significant association between virological response and Ctrough (p-value .034) with an increase of 0.1 mg/L corresponding to a 2.96 reduction in the risk of having a detectable viral load. The results indicated that in pregnant women a RAL Ctrough threshold of 0.04 mg/L has a higher specificity (75%) as compared to our current Ctrough target value of 0.02 mg/L (25%) and an acceptable sensitivity (77%). No significant differences were observed between Ctrough at each trimester. When comparing pregnancies with and without TDM, no statistically significant differences were observed in the virologic response during pregnancy and at delivery, or with the need for triple antiretroviral prophylaxis in newborns. CONCLUSIONS: An association between RAL Ctrough and viral load was observed and achieving a RAL Ctrough of 0.04 mg/L or greater is a predictor of virologic response in pregnant women. The impact of TDM in pregnancy, however, could not be demonstrated.

Short communication: Is there any benefit of initiating aspirin before the 11th week of gestation?

Aspirin initiated between 11 and 14 weeks of gestation reduces the risk of preterm preeclampsia and other placenta-mediated complications in screen-positive women. Most of these adverse outcomes are associated with maternal vascular malperfusion of the placenta, a disease that begins during the early first trimester. Assuming that aspirin has direct beneficial actions on the developing placenta, tempts clinicians to believe in the maxim that "the earlier the better", however neither the safety nor the effectiveness of aspirin started before 11th week of gestation has been demonstrated. Therefore, outside of research protocols, aspirin should not be started before the 11th week of pregnancy for the prevention of preeclampsia.

The Impact of COVID-19 on Maternal Mental Health during Pregnancy: A Comparison between Canada and China within the CONCEPTION Cohort.

The effect of the COVID-19 pandemic on maternal mental health has been described in Canada and China but no study has compared the two countries using the same standardized and validated instruments. In this study, we aimed to evaluate and compare the impact of COVID-19 public health policies on maternal mental health between Canada and China, as we hypothesize that geographical factors and different COVID-19 policies are likely to influence maternal mental health. Pregnant persons >18 years old were recruited in Canada and China using a web-based strategy. All participants recruited between 26 June 2020 and 16 February 2021 were analyzed. Self-reported data included sociodemographic variables, COVID-19 experience and maternal mental health assessments (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7) scale, stress and satisfaction with life). Analyses were stratified by recruitment cohort, namely: Canada 1 (26 June 2020-10 October 2020), Canada 2 and China (11 October 2020-16 February 2021). Overall, 2423 participants were recruited, with 1804 participants within Canada 1, 135 within Canada 2 and 484 in China. The mean EDPS scores were 8.1 (SD, 5.1) in Canada 1, 8.1 (SD, 5.2) in Canada 2 and 7.7 (SD, 4.9) in China (p-value Canada 2/China: p = 0.005). The mean GAD-7 scores were 2.6 (SD, 2.9) in China, 4.3 (SD, 3.8) in Canada 1 (p < 0.001) and 5.8 (SD, 5.2) in Canada 2 (p < 0.001). When adjusting for stress and anxiety, being part of the Chinese cohort significantly increased the chances of having maternal depression by over threefold (adjusted OR 3.20, 95%CI 1.77-5.78). Canadian and Chinese participants reported depressive scores nearly double those of other crises and non-pandemic periods. Lockdowns and reopening periods have an important impact on levels of depression and anxiety among pregnant persons.

Pharmacokinetics of Cannabis and Its Derivatives in Animals and Humans During Pregnancy and Breastfeeding.

Cannabis is one of the most widely used illicit drugs during pregnancy and lactation. With the recent legalization of cannabis in many countries, health professionals are increasingly exposed to pregnant and breastfeeding women who are consuming cannabis on a regular basis as a solution for depression, anxiety, nausea, and pain. Cannabis consumption during pregnancy can induce negative birth outcomes such as reduced birth weight and increased risk of prematurity and admission to the neonatal intensive care unit. Yet, limited information is available regarding the pharmacokinetics of cannabis in the fetus and newborn exposed during pregnancy and lactation. Indeed, the official recommendations regarding the use of cannabis during these two critical development periods lack robust pharmacokinetics data and make it difficult for health professionals to guide their patients. Many clinical studies are currently evaluating the effects of cannabis on the brain development and base their groups mostly on questionnaires. These studies should be associated with pharmacokinetics studies to assess correlations between the infant brain development and the exposure to cannabis during pregnancy and breastfeeding. Our project aims to review the available data on the pharmacokinetics of cannabinoids in adults, neonates, and animals. If the available literature is abundant in adult humans and animals, there is still a lack of published data on the exposure of pregnant and lactating women and neonates. However, some of the published information causes concerns on the exposure and the potential effects of cannabis on fetuses and neonates. The safety of cannabis use for non-medical purpose during pregnancy and breastfeeding needs to be further characterized with proper pharmacokinetic studies in humans feasible in regions where cannabis has been legalized. Given the available data, significant transfer occurs to the fetus and the breastfed newborn with a theoretical risk of accumulation of products known to be biologically active.

The COVID-19 Pandemic Impacted Maternal Mental Health Differently Depending on Pregnancy Status and Trimester of Gestation.

Introduction: We aimed to measure the impact of the COVID-19 pandemic on maternal mental health, stratifying on pregnancy status, trimester of gestation, and pandemic period/wave. Methods: Pregnant persons and persons who delivered in Canada during the pandemic, >18 years, were recruited, and data were collected using a web-based strategy. The current analysis includes data on persons enrolled between 06/2020−08/2021. Maternal sociodemographic indicators, mental health measures (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7), stress) were self-reported. Maternal mental health in pregnant women (stratified by trimester, and pandemic period/wave at recruitment) was compared with the mental health of women who had delivered; determinants of severe depression were identified with multivariate logistic regression models. Results: 2574 persons were pregnant and 626 had already delivered at recruitment. Participants who had delivered had significantly higher mean depressive symptom scores compared to those pregnant at recruitment (9.1 (SD, 5.7) vs. 8.4 (SD, 5.3), p = 0.009). Maternal anxiety (aOR 1.51; 95%CI 1.44−1.59) and stress (aOR 1.35; 95%CI 1.24−1.48) were the most significant predictors of severe maternal depression (EDPS ˃ 13) in pregnancy. Conclusion: The COVID-19 pandemic had a significant impact on maternal depression during pregnancy and in the post-partum period. Given that gestational depression/anxiety/stress has been associated with preterm birth and childhood cognitive problems, it is essential to continue following women/children, and develop strategies to reduce COVID-19's longer-term impact.

Mifepristone-Misoprostol Use for Second- and Third-Trimester Medical Termination of Pregnancy in a Canadian Tertiary Care Centre.

OBJECTIVE: This study aims to evaluate the impact of the implementation a mifepristone-misoprostol protocol (MIFE/MISO) on the induction-to-expulsion interval in the context of second- and third-trimester pregnancy termination or intrauterine fetal death (IUFD) compared with misoprostol alone (MISO), and to share the experience of a Canadian tertiary hospital concerning the feasibility and safety of such a protocol. METHODS: This is a single-centre retrospective pre-post cohort study carried out at the Centre Hospitalier Universitaire (CHU) Sainte-Justine between 2017 and 2019. Women in the MIFE/MISO group were instructed to take mifepristone 24-48 hours before induction. Induction in the MIFE/MISO group was performed with misoprostol dosages adjusted to gestational age and the presence of previous uterine scars, while, in the MISO group, all patients received 400 µg of misoprostol vaginally every 4 hours. RESULTS: Ninety-four patients were included in the MIFE/MISO group and 103 patients, in the MISO group. Median time to expulsion was significantly lower in the MIFE/MISO group than the MISO group (13.5 and 19.5 h respectively; P < 0.001). The total dose of misoprostol administered was significantly lower in the MIFE/MISO group than the MISO group, and adverse effects were reported in 60% and 82% of patient records, respectively (P < 0.001). Complication rates were similar between the 2 groups. CONCLUSION: The MIFE/MISO protocol is highly effective for second- and third-trimester induction for pregnancy termination or IUFD, without increasing complication rates and with fewer reported adverse effects. Its implementation is safe and feasible in a tertiary medical centre.

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.

Simultaneous quantification of 19 analytes in breast milk by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

A bioanalytical method by high performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS) for the simultaneous quantification of 17 drugs and 2 major active metabolites in breast milk was developed and validated. Breast milk samples (100 µL) were submitted to a simple protein precipitation for the extraction of the analytes after the addition of deuterated internal standards (10 µL). A Kinetex C8 column was used for the separation of analytes with mobile phases composed of acetonitrile with 0.1 % formic acid and water with 0.1 % formic acid in gradient elution mode. Analytes were detected using an AB/SCIEX 4000 QTRAP instrument with positive electrospray ionization and operating in scheduled multiple reaction monitoring mode. Validation covered a large range of concentrations (0.5-500 ng/mL) for most of the analytes except bisoprolol, lacosamide, vilazodone (1-500 ng/mL), acid mycophenolic, letrozole, clomiphene (2-500 ng/mL) and hydroxy-melatonin (10-500 ng/mL). Within-run and between-run accuracy and precision for 4 levels of quality controls (QC) spiked at the lower limit of quantification (LLOQ), at 3 times the LLOQ, 50 % of the upper limit of quantification (ULOQ) and 80 % of the ULOQ were in agreement with the criteria from international guidelines. Matrix effect and extraction recovery ranged from 40.7 to 106.5 % and 87.3 to 110.8 %, respectively with relative standard deviations less than 15 %. Furthermore, all analytes were stable in breast milk at room temperature for 24 h, at -20 °C for two weeks, at -80 °C for 1 month, and after 3 freeze-thaw cycles. Finally, the method was successfully applied to nursing women samples collected from an ongoing feasibility study on drug quantification in breast milk.

Evaluation of cabergoline for lactation inhibition in women living with HIV.

We wished to evaluate the efficacy, safety, and acceptability of cabergoline for lactation inhibition in women who live with HIV. In this multicenter prospective observational study, cabergoline was offered as a single oral dose of 1 mg within the first 48 h postpartum. Women were recruited if they delivered a live infant after 35 weeks of gestational age. Participants filled out a questionnaire regarding symptoms of lactation and cabergoline adverse effects on day 2 and day 14 postpartum. On day 14, they also completed a questionnaire about their satisfaction with cabergoline treatment. Prolactin serum level was measured on both visits. Among 68 participants, all but one received cabergoline. The overall effectiveness defined by partial or complete success at day 14 was 98.3% (confidence intervals: 89.5-99.9). At day 14, 67.4% of women who received cabergoline had prolactin serum levels <25 mcg/L (threshold necessary for galactopoiesis). Mild nonspecific adverse effects were experienced by 24 (29.9%) women on day 2 and 24 (41.4%) on day 14, and lasted 48 h or less. Overall, 96% of women were satisfied with cabergoline's ability to prevent postpartum lactation symptoms. In conclusion, cabergoline is an effective, well-accepted, and well-tolerated medication for lactation inhibition in WLWH.

A Pilot Randomized Trial Comparing the Effects of 80 versus 160 mg of Aspirin on Midtrimester Uterine Artery Pulsatility Index in Women with a History of Preeclampsia.

OBJECTIVE: To compare the effects of 80 mg and 160 mg of aspirin, initiated in the first trimester of pregnancy, on mid-trimester uterine artery pulsatility index (UtA-PI) in women with a history of preeclampsia. METHODS: We performed a pilot double-blind randomized controlled trial. Pregnant women with a history of preeclampsia were recruited between 100/7 and 136/7 weeks gestation and randomly assigned to take either 80 or 160 mg of aspirin daily at bedtime from randomization to 356/7 weeks gestation. The primary outcome was mean UtA-PI at 22-24 weeks. Secondary outcomes included the rate of fetal growth restriction and preeclampsia, stratified as term (≥37 weeks), preterm (<37 weeks), and early-onset (<34 weeks) preeclampsia. RESULTS: A total of 107 participants were randomized, including 41 (38%) with a history of preterm preeclampsia and 16 (15%) with a history of early-onset preeclampsia. We observed no significant difference in mean UtA-PI at 22-24 weeks between the 2 groups (0.97; 95% CI 0.88-1.05 vs. 0.97; 95% CI 0.88-1.07, P = 0.9). The rates of fetal growth restriction (8% vs. 2%; P = 0.20); preeclampsia (12% vs. 15%; P = 0.78), preterm preeclampsia (4% vs. 2%; P = 0.56), and early-onset preeclampsia (0% vs. 2%; P = 0.52) were similar in both groups. No serious adverse events associated with the study treatment were reported. CONCLUSION: We observed no significant difference in UtA-PI between the two doses of aspirin, but we observed low rates of fetal growth restriction and preterm and early-onset preeclampsia (all less than 5%). The benefits of aspirin for the prevention of preterm preeclampsia is probably not related to the improvement of deep placentation alone.

Infant Exposure to Methylphenidate and Duloxetine During Lactation.

BACKGROUND: Duloxetine and methylphenidate are commonly prescribed for the management of depression and attention-deficit/hyperactivity disorder (ADHD), respectively. However, little information is available concerning their safety during lactation. The purpose of this case series was to provide additional information to the medical literature concerning infant exposure to methylphenidate and duloxetine through breast milk. METHOD: Bioanalytical method (liquid chromatography coupled to mass spectrometry) was developed and validated before its use to determine the concentrations of both medications in breast milk samples. CASES: Case 1: A 30-year-old woman with depression and ADHD took duloxetine 90 mg daily and methylphenidate 36 mg daily during pregnancy and breastfeeding. The newborn was found to have a congenital pulmonary airway malformation. The breastfeeding status was nonexclusive. At week 4 postpartum, the concentration found in the milk was 32.8 ng/mL of duloxetine and 7.9 ng/mL of methylphenidate (estimated relative infant dose [RID] of 0.3% and 0.2%, respectively). Case 2: A 41-year-old women with depression took duloxetine 60 mg daily during pregnancy and lactation. She gave birth to a healthy child. The breastfeeding status was nonexclusive. Cord to maternal plasma concentration ratio was 0.4. At day 6 postpartum, the concentration of duloxetine was 23.6 ng/mL in the foremilk and 14.3 ng/mL in the hindmilk (RID of 0.4% and 0.2%, respectively). At week 6 postpartum, the concentration was 25.2 ng/mL in the foremilk and 29.3 ng/mL in the hindmilk (RID of 0.4% and 0.4%, respectively). CONCLUSION: In accordance with previously published data, this case series suggests a minimal exposure to duloxetine and methylphenidate through breast milk. Thus, these drugs are likely compatible with lactation. However, large cohort studies are necessary to evaluate their long-term impact on the exposed infants.

Self-administered medications in the postpartum wards: A study on satisfaction and perceptions.

OBJECTIVE: The objective of this study was to describe women's satisfaction and perceptions on the postpartum self-administered medication (SAM) program at our institution and on pain relief. Also, we aimed at describing maternal and breastfed infants' adverse events with the use of the postpartum SAM program. METHOD: This prospective 1-group mixed methods survey conducted in a mother-and-child tertiary center included women enrolled in the postpartum SAM program who had a live newborn, understood French or English, and were at least 18 years old. Newborns included cohabited with their mother during their hospitalization and had received breast milk at least once. Data were collected through direct interviews using a questionnaire and through medical charts. RESULTS: We included 314 mothers and 263 breastfed newborns in the study. Ninety-seven percent of all users appreciated the SAM. The self-reported median overall improvement of pain was 80% (interquartile range, 70%-90%). However, 18% of users who delivered vaginally and 32% who delivered through caesarean would have preferred traditional drug dispensing by the nurse (P = .009). Drugs used in the SAM program were generally well tolerated. There were no worrisome adverse drug events reported in newborns' medical charts. CONCLUSION: Results show a 97% rate of satisfaction of the SAM program and a high self-reported pain improvement in a cohort of 314 women using our SAM program. The results suggest that the SAM program should remain a standard practice in our institution. Some recommendations will be drawn to better tailor the SAM program to the needs expressed by the users.

Impact of Azithromycin on Pregnancy Prolongation in Women at Risk of Preterm Labor: A Time-to-Event Analysis.

BACKGROUND: Since 2006, the empiric use of azithromycin in women at risk of premature birth has become prevalent in our institution without any evidence of its efficacy. Although antibiotics can prolong pregnancy in preterm prolonged rupture of membranes, no published data are available for women with intact membranes. OBJECTIVES: To describe the purpose of adding azithromycin to the usual treatments (cerclage, tocolysis, rest, etc.) to prolong pregnancy in women with intact membranes who are at risk of or already in preterm labour. METHODS: A retrospective observational cohort study was done at a Mother-Child University Hospital Centre. Patients admitted to obstetric ward who received azithromycin between January 1st, 2006 and August 1st, 2010 were included. A total of 127 exposed women were matched to 127 controls through medical records and pharmacy software. A time-to-event analysis was done to compare gestational age at the time of the recorded composite event (delivery, or rupture of membranes, or second intervention to prolong pregnancy). To compare proportions of composite event at different time points, χ2 tests were used. RESULTS: Patients who received azithromycin had a more severe condition at presentation. Once adjusted for confounding factors, prolongation of pregnancy (HR =1.049; CI 95%: 0.774-1.421 [p=0.758]) and gestational age at the event (HR=1.200; CI 95%: 0.894-1.609 [p=0.225]) did not differ between the groups. The proportions of women with an event ≥7 days post-diagnosis or ≥37 gestational weeks were similar. CONCLUSIONS: Azithromycin was added to medical therapy in a more at-risk population and no clear benefit was measured.

Systematic procedure for the classification of proven and potential teratogens for use in research.

BACKGROUND: Although there is strong evidence that some medications are teratogenic, the current lists of teratogens to be used in research are outdated. The objective of this study was to develop an updatable and systematic procedure to the classification of medications proven and potentially teratogenic in the first trimester of pregnancy, for use in research. METHODS: We developed a two-step procedure for teratogen classification. Step 1 includes classifying the medications from Drugs in Pregnancy and Lactation: a Reference Guide to Fetal and Neonatal Risk (9th ed.) into two provisional lists: (1) teratogenic medications, and (2) potentially teratogenic medications. We also searched other references to add other medications. In Step 2, the Teratology Information System (TERIS) database was searched, and the medication was classified as teratogenic or potentially teratogenic according to a newly developed scheme. Expert consensus was used if a medication was not recorded in TERIS. RESULTS: A total of 114 medications were identified in Drugs in Pregnancy and Lactation: a Reference Guide to Fetal and Neonatal Risk, with 57 medications in each provisional list. Seventy-eight medications were identified in other sources. A total of 135 medications were included in Step 2; the TERIS scheme classified 23 medications, and 112 medications required expert opinion. The two experts agreed on 78.6% of the medications (kappa = 0.63). We identified 91 teratogenic and 81 potentially teratogenic medications. CONCLUSION: Using reliable references, we established a systematic procedure to the classification of medications with evidence of or potential teratogenic risk. These exhaustive lists will be useful in teratology research and related fields.