Short- and long-term complications of in utero exposure to lamotrigine.

AIMS: The present study evaluates the effect of antenatal lamotrigine exposure, on short- and long-term paediatric outcome. METHODS: The study included the children of 83 epileptic women treated with lamotrigine during pregnancy, at a tertiary medical centre between 2004-2014. All newborns were monitored for vital signs, congenital malformations and Finnegan score. In addition, the parents completed a questionnaire regarding their child's development and health up to the age of 12 years. RESULTS: No major malformations were found in the newborns. None of the newborns had significant withdrawal symptoms by Finnegan score. The children were followed-up to the age of 12 years (56.6% were 6-12 years at the time of evaluation). There were no significant findings in the incidence of neurodevelopmental disorders. CONCLUSIONS: According to our experience, lamotrigine is generally safe for pregnancy use, associated with minimal short-term complications with no long-term effects on the outcome.

For Debate: Does Cannabis Use by the Pregnant Mother Affect the Fetus and Newborn?

Cannabis, commonly called marijuana, is often used during pregnancy, likely due to the perception that it is a "safe" drug. Changes in legislation in many countries have lead to the increased availability of this drug and to its increasing use during pregnancy, often with other concomitant exposures such as alcohol, tobacco, and other drugs. Herein, we review the medical literature regarding effects of marijuana on the fetus and newborn. Possible effects of in utero exposure to marijuana focus on fetal growth, increase in the rates of stillbirth and preterm delivery, congenital malformations, and neurodevelopmental effects on the child. Published studies for all these outcomes are inconsistent. Fetal weight growth may be somewhat decreased, but the magnitude of this decrease is no greater than 100 g. There is insufficient evidence to conclude on any effect on the stillbirth rate. Although there are some reports of a slight increase in the rate of prematurity, most reports do not support this effect. Marijuana does not appear to be a major teratogen; however, a small increased risk for some congenital birth defects may be associated with early pregnancy use. Neurodevelopmental effects have been associated with marijuana use, but it is difficult to control for the effect of confounders. Despite the lack of conclusive evidence, it is important to remember that marijuana has not been shown to be a harmless drug during pregnancy and may affect the long-term neurodevelopment of the newborn infant.

Outcome of breastfed infants following post-partum methylergonovine treatment.

OBJECTIVE: To evaluate maternal and breastfed infant's outcome following post-partum maternal use of methylergonovine. METHODS: A prospective, controlled observational study design was used. Mothers who contacted Beilinson Teratology Information Service (BELTIS) were followed by phone interview. Data on lactation, neonatal symptoms and outcomes at the age of 1-3 years were obtained. Mothers' breastfeeding while treated with methylergonovine and their infants were compared to a matched control group of breastfeeding mothers using a drug known to be safe during lactation (amoxicillin). RESULTS: Follow-up was obtained for 38 of 42 women (90.5%). Of whom, six stopped breastfeeding because of concerns regarding drug treatment and three refused to participate. The remaining 29 women and infant pairs were compared to a control group of 58 women and their infants. Comparison showed no effect of methylergonovine on lactation and similarly showed no difference in rate of neonatal complications (p = 1). At time of follow-up there were no differences in growth or in adverse neurodevelopment outcomes (p = 0.26). CONCLUSIONS: No increase in adverse long-term outcomes was found in infants exposed to methylergonovine through breastfeeding. Our data in conjunction with previous estimates of very low drug exposure support continuation of breastfeeding in women requiring treatment with methylergonovine.

Colchicine use during breastfeeding.

OBJECTIVE: This study evaluated the outcome of infants exposed to colchicine during lactation. SUBJECTS AND METHODS: A prospective observational cohort study design was used. Mothers who contacted Beilinson Teratology Information Service (BELTIS) regarding use of colchicine while breastfeeding were followed up by phone interview. Data on lactation, neonatal symptoms, and outcome 1-3 years after initial consultation were obtained. Mothers breastfeeding while taking colchicine (n=37) and their infants (n=38) were compared with a matched control group of mothers using a drug known to be safe during lactation (n=75) and their infants (n=76). RESULTS: Follow-up was obtained for 59 of 76 (78%) women who contacted BELTIS regarding use of colchicine. Of the 59 women, 37 breastfed while taking colchicine, five did not take colchicine, 16 did not breastfeed, and one declined to participate. The mean duration of breastfeeding was similar in both groups. Adverse neonatal symptoms were seen in three of 38 colchicine-exposed infants versus four of 76 of control group infants (p=0.68). Delayed development or neurological abnormalities were seen in two infants in both study groups (p=0.60). None of the colchicine-exposed infants showed abnormal growth. CONCLUSIONS: No increase in adverse long-term outcomes was found in colchicine-exposed breastfed infants. Our data support continuation of breastfeeding in women treated with colchicine.

Outcome following tranexamic acid exposure during breastfeeding.

OBJECTIVE: This study evaluated the outcome of infants exposed to tranexamic acid during lactation. SUBJECTS AND METHODS: A prospective, controlled observational study design was used. Mothers who contacted the Beilinson Teratology Information Service (BELTIS) regarding use of tranexamic acid while breastfeeding were followed up by phone interview. Data on lactation, neonatal symptoms, and outcomes at the age of 1-3 years were obtained. Mothers' breastfeeding while taking tranexamic acid and their infants were compared with those of a matched control group of breastfeeding mothers using a drug known to be safe during lactation (amoxicillin) and their infants. RESULTS: Follow-up was obtained for 28 of 32 women who sought advice regarding use of tranexamic acid during breastfeeding. Of the 28 women, six did not take the drug, and one refused to participate. The 21 remaining women (study group) were compared with 42 control women. A decreased amount of breastmilk was reported by one woman in the study group versus two women in the control group (p=1.0). Possible adverse drug effects were reported for one of 21 study group infants (restlessness) and for one of 42 control group infants (gastroesophageal reflux) (p=1.0). Growth below the 3rd percentile was found in one of 21 study group infants versus four of 42 control group infants (p=0.66). Development was normal for all study group infants. CONCLUSIONS: No increase in adverse long-term outcomes was found in infants exposed through breastfeeding to tranexamic acid. Our data in conjunction with previous estimates of very low drug exposure support continuation of breastfeeding in women requiring treatment with tranexamic acid.

Antipsychotic drugs and breastfeeding.

OBJECTIVE: The incidence of psychotic disorders during the postpartum period is higher than at any other time during a women's life and coincides with the time when breastfeeding is most recommended. As a result, safety data on use of antipsychotic drugs during lactation is essential. Our aim was to analyze the medical literature for information on antipsychotic drug use during breastfeeding and to determine the safety of their use for the exposed infant. DATA SOURCES: Medline (U.S. National Library of Medicine), LactMed (U.S. National Library of Medicine) and Reprotox (Reproductive Toxicology Center) databases were searched to identify all relevant medical literature on antipsychotic medications and lactation. The database search, updated to March, 2012, used the generic name of each antipsychotic drug in combination with the terms breastfeeding or lactation or breast-milk. STUDY SELECTION: 4 prospective studies, 12 case series, 28 case reports and 1 pharmaceutical registry were included. DATA EXTRACTION: Infant outcomes focusing on long-term outcome were summarized from all reports of breastfeeding mothers taking antipsychotic medications. Recommendations for drug use during breastfeeding were based on safety data and on pharmaco kinetic drug properties. Recommendatins were categorized as acceptable, possible under medical supervision, or, not recommended. RESULTS: Among 21 antipsychotic drugs used in clinical practice, for 7 there are no data at all regarding breastfeeding and for 6 others the data are based only on few infant exposures. Only few prospective studies assessing'use of haloperidol, chlorpromazine and olanzapine during breastfeeding were identified. Olanzapine and quetiapine were categorized as acceptable for breastfeeding. Chlorpromazine, haloperidol, risperidone and zuclopenthixol were categorized as possible for breastfeeding under medical supervision. Breastfeeding cannot be currently recommended for the following medications: aripiprazole, asenapine, chlorprothixene, clozapine, droperidol, fluphenazine, flupenthixol, iloperidone, lurasidone, paliperidone, perphenazine, pimozide, trifluoperazine, thiothixene and ziprasidone. CONCLUSIONS: With a limited number of infants exposed to antipsychotic drugs during breastfeeding, for most drugs a firm and evidence-based conclusion cannot be reached. Counseling of breastfeeding mothers should be carefully assessed. Pharmacokinetic drug characteristics, disease severity, behavioral or psychosocial alternatives, preventative interventions and possible impact of discontinuing breastfeeding on the maternal-infant relationship should all be considered.

Evaluation of the efficacy and safety of bi-daily combination therapy with pyridoxine and doxylamine for nausea and vomiting of pregnancy.

BACKGROUND: Diclectin (pyridoxine 10 mg and doxylamine 10 mg) has traditionally been used to treat nausea and vomiting of pregnancy (NVP); however, this drug is unavailable in many countries. OBJECTIVES: To evaluate the efficacy and safety of a simple bi-daily treatment regimen with the combination of pyridoxine (50 mg twice daily) and doxylamine (25-50 mg) as an alternative treatment for NVP. METHODS: A prospective case-controlled observational study of mother-infant pairs was conducted between February 2008 and December 2010. All women who contacted the Beilinson Teratology Information Service (BELTIS) regarding treatment of NVP were eligible for inclusion. Using data on NVP severity, treatment efficacy and outcomes, we compared the two groups of women: those treated with the combination of pyridoxine and doxylamine (treatment group, n=29) and those treated with metoclopramide (control group, n=29). RESULTS: Moderate to severe symptoms were present in 97% of the treatment group women vs. 69% of control group women (P < 0.01). Despite increased symptom severity in the treatment group, the combination regimen was efficacious: 20/29 (69%) vs. 18/25 (72%) in the treatment vs. control women respectively (P = 0.65). There were no congenital anomalies in the treatment group. Follow-up was normal for all infants. CONCLUSIONS: Bi-daily combination therapy with pyridoxine and doxylamine for NVP is safe, has comparable efficacy to metoclopramide, and is a treatment alternative in countries where Diclectin is not available. Despite symptoms warranting counseling by a teratology information service, more than a third of women do not take the suggested treatment.

Levonorgestrel used for emergency contraception during lactation-a prospective observational cohort study on maternal and infant safety.

OBJECTIVE: To identify possible effects of levonorgestrel used as an emergency contraceptive during breastfeeding on mothers and their infants. STUDY DESIGN: A prospective observational cohort study of all women who contacted the Teratology Information Service between January, 2005 and January, 2010. Breastfeeding women who used levonorgestrel as an emergency contraceptive (study group) were compared to breastfeeding women who used either ethynodiol diacetate or desogestrel (control group). Women were followed for 6-24 months. Main outcome measures were adverse maternal and infant effects and continuation of breastfeeding. RESULTS: We followed 71 of 128 study group women and 72 of 100 control group women. Maternal adverse effects were mainly vaginal bleeding, which was less frequent in the study vs. control group (16 of 71 vs. 27 of 72, p = 0.068). Decreased lactation was uncommon and similar in both groups. Breastfeeding was reinitiated within less than 8 h in 75% of the levonorgestrel group women. Adverse infant effects were rare (0 of 72 infants vs. 2 of 72 infants, p = 0.5 in the study vs. control group). CONCLUSIONS: Our findings support the safety of using levonorgestrel as an emergency contraceptive during lactation without the need for withholding breastfeeding.

The outcomes of pregnancy in women exposed to the new macrolides in the first trimester: a prospective, multicentre, observational study.

BACKGROUND: Macrolides are a group of commonly prescribed antibiotics. There is some doubt surrounding the use of the newer macrolides in pregnancy. OBJECTIVE: The present study aimed to compare outcomes of pregnancies exposed to the new macrolides clarithromycin, azithromycin and roxithromycin with non-teratogenic preparations. METHODS: In this prospective, multinational, multicentre, controlled, observational study, information was obtained either from pregnant women or their healthcare professionals who contacted their local teratogen information services in Italy, Israel, the Czech Republic, the Netherlands and Germany seeking information after exposure to macrolides. The comparison group included women or their healthcare professional who contacted these centres with questions regarding known non-teratogenic preparations. Information on obstetric and other background parameters was collected at enrollment; after delivery, subjects or their healthcare professionals were contacted to ascertain pregnancy outcome parameters and other exposures through the remainder of the pregnancy. RESULTS: A total of 608 women exposed to macrolides during pregnancy were enrolled; 511 of the exposures occurred during the first trimester. The comparison group comprised 773 women exposed to non-teratogenic preparations during the first trimester of pregnancy. No significant difference in the rate of major congenital malformations was found between the study group and the comparison group (3.4% vs 2.4%; p = 0.36; odds ratio (OR) 1.42; 95% CI 0.70, 2.88) or in the rate of cardiovascular malformations (1.6% vs 0.9%; p = 0.265; OR 1.91; 95% CI 0.63, 5.62). No significant differences were found between subgroups of macrolides in the rates of major congenital malformations or cardiac malformations, although for azithromycin this was of borderline significance. CONCLUSIONS: This study, in agreement with earlier smaller studies, suggests that the new macrolides do not pose a significantly increased risk of major congenital malformations or cardiac malformations.

Pregnancy outcome following exposure to topical retinoids: a multicenter prospective study.

Concerns have been raised about the use of topical retinoids since the publication of isolated cases of characteristic retinoid embryopathy, originally described after oral use. A collaborative study of the European Network of Teratology Information Services was carried out to evaluate the rate of congenital malformations following first-trimester topical retinoid exposure. A population of 235 exposed pregnant women was compared with 444 controls. No significant differences were observed between groups with regard to the rates of spontaneous abortion (odds ratio [95% confidence interval], 1.5 [0.8-2.7]), minor birth defects (1.3 [0.4-3.7]), and major birth defects (1.8 [0.6-5.4]). No child showed features of retinoid embryopathy. The rate of elective termination in the exposed group was increased 3-fold (3.4 [1.5-7.8]). In conclusion, these results do not suggest an increased risk of retinoid embryopathy. However, according to current knowledge, topical retinoids cannot be advised for use during pregnancy because their risk/benefit ratio remains questionable.

17α Hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth.

Use of 17-alpha-hydroxyprogesterone caproate for the prevention of spontaneous preterm birth in women at risk is reviewed. Early studies regarding this topic reached contradicting conclusions, however recent studies showed that weekly injections of 17-alpha-hydroxyprogesterone caproate beginning at 16-20 weeks' gestation resulted in a substantial reduction in the rate of spontaneous recurrent preterm birth. Long-term follow-up of children exposed in-utero to the drug has shown normal growth and development and normal scores for gender specific roles. In conclusion, 17-alpha-hydroxyprogesterone caproate is currently the only drug with sufficient evidence to support its use for prevention of spontaneous recurrent preterm birth.

Outcome of infants exposed to olanzapine during breastfeeding.

OBJECTIVE: This study evaluated the outcome of infants exposed to olanzapine during lactation. METHODS: A prospective, controlled observational study design was used. Mothers who contacted Beilinson Teratology Information Service regarding use of olanzapine while breastfeeding were followed by phone interview. Data on lactation, neonatal symptoms, and outcome at the age of 1-2 years were obtained. Mother-infant groups were compared. Mothers breastfeeding while taking olanzapine (n = 22) were compared to two control groups of mothers who continued to take olanzapine but did not breastfeed (n = 15) and to breastfeeding mothers using a drug known to be safe during lactation (n = 51). RESULTS: Follow-up was obtained for 37 of 70 women. Comparison of olanzapine-exposed breastfed versus control breastfed infants showed a similar duration of breastfeeding; however, early discontinuation of breastfeeding was more common in the olanzapine-exposed breastfed group (five of 22 vs. none of 51, p = 0.02). The rate of adverse outcomes in olanzapine-exposed breastfed infants did not differ from those of the control groups. Among the 30 newborns exposed in utero to olanzapine, no congenital birth defects were found. Neonatal symptoms were seen in six of 30 of olanzapine-exposed infants versus two of 51 of nonexposed infants (p < 0.05). A withdrawal syndrome was seen in three of 30 (10%) infants. CONCLUSIONS: No increase in adverse long-term outcomes in olanzapine-exposed breastfed infants were found. Our data in conjunction with previous estimates of very low drug exposure support continuation of breastfeeding in women treated with olanzapine. However, until additional long-term studies are available, infants exposed to olanzapine through breastmilk should be followed up.

Are selective serotonin reuptake inhibitors cardiac teratogens? Echocardiographic screening of newborns with persistent heart murmur.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been suspected of cardiac teratogenicity, but reports have been inconsistent. Our aim was to investigate the rate of nonsyndromic congenital heart defects in newborns exposed in utero to SSRIs compared with unexposed controls. METHODS: This prospective study of women who gave birth at our tertiary center from 2000 to 2007 yielded 235 women who reported first-trimester SSRI use during pregnancy. All newborns born during the study period and found to have a persistent cardiac murmur on day 2 or 3 of life were referred for examination by a pediatric cardiologist and by echocardiography. The findings were compared between the newborns who were exposed to SSRIs and those who were not. RESULTS: Nonsyndromic congenital heart defects were identified by echocardiography in 8 of 235 (3.40%) newborns exposed in utero to SSRIs and in 1083 of 67,636 (1.60%) non-exposed newborns. The difference in prevalence between the two groups was significant (relative risk, 2.17; 95% confidence interval, 1.07-4.39). The prevalence rates for paroxetine and fluoxetine exposure were 4.3% and 3.0%, respectively. All cardiac defects in the study group were mild: ventricular septal defect (6), bicuspid aortic valve (1) and right superior vena cava to coronary sinus (1). CONCLUSIONS: Newborns exposed in utero to SSRIs, have a twofold higher risk of mild nonsyndromic heart defects than unexposed infants. The data suggest that women who require SSRI treatment during pregnancy can be reassured that the fetal risk is low and possible cardiac malformations will probably be mild. Late-targeted ultrasound and fetal echocardiography at 22 to 23 weeks' gestation are recommended in this patient group.

Tetrada of the possible mycophenolate mofetil embryopathy: a review.

Mycophenolate mofetil (MFM) is an immunosuppressant agent used in organ transplantation, rheumatoid arthritis and lupus nephritis. Experimental data show that doses roughly equivalent to those used clinically in transplant patients may cause fetal resorption and malformations in pregnant rats and rabbits. There are limited data regarding the use of MFM in pregnant women. The human experience is based on 9 case reports, 1 case series, and 2 registry data. The most frequent structural anomalies described in 12 newborns exposed to MFM were as follows: microtia (11); auditory canal atresia (8); cleft lip and palate (6); micrognathia (4); hypertelorism (4); ocular coloboma (3); short fingers (2) and hypoplasic nails (2). The distinctive and unique phenotype associated with MFM exposure during pregnancy (EMFO tetrada: Ear, Mouth, Fingers, Ocular/Organ malformation) raised the hypothesis that MFM may be a real teratogenic drug. Appropriate recommendations to prevent this possible new embryopathy are given.

The safety of amoxicillin/clavulanic acid and cefuroxime during lactation.

Breast-feeding is considered the gold standard for infant nutrition. In spite of statements about the safe use of drugs in lactation by the American Academy of Pediatrics, medical professionals remain confused regarding the management of drug therapy in nursing mothers, and this can lead to suboptimal prescribing and poor compliance. The aim of our study was to evaluate the safety of 2 of the newer antibiotics, amoxicillin/clavulanic acid and cefuroxime, during lactation. Breast-feeding women who called a drug consultation center to obtain information about the potential risks of amoxicillin/clavulanic acid (67 women) and cefuroxime (38 women) were prospectively recruited. As a control group, women who were treated with antibiotics known to be safe during lactation were recruited: amoxicillin (n = 40) for the amoxicillin/clavulanic acid group and cephalexin (n = 11) for the cefuroxime group. Women in the control group were matched for indication for antibiotic therapy, duration of treatment, and maternal age. Participants were interviewed after treatment termination regarding adverse reactions during therapy. In the amoxicillin/clavulanic acid group, 15 infants (22.3%) had adverse effects, and the rate increased with dosage (P = 0.0139). This was significantly higher than the amoxicillin group, where 3 infants (7.5%) had adverse effects (P = 0.046, relative risk (RR) = 2.99, 95% confidence interval (CI) 0.92-9.68). However, there were no significant differences between rates of specific events. The rate of adverse effects in the cefuroxime group (2.6%) was not significantly different from that in controls (9%) (P = 0.58, OR = 0.92, 95% CI 0.94-1.06). All adverse effects were minor, self-limiting, and did not necessitate interruption of breast-feeding. Our data suggest that amoxicillin/clavulanic acid and cefuroxime may be safe during lactation. Larger studies are needed to confirm these findings.

Paroxetine during breast-feeding: infant weight gain and maternal adherence to counsel.

UNLABELLED: The aims of the present study were to examine the weight gain in infants breast fed by mothers taking paroxetine and to assess the clinical implementation of the recommendations of the teratology service in our centre. A prospective cohort study design was used. The study group included 27 mothers who had taken paroxetine for at least 2 weeks while breast-feeding, 19 mothers who did not taken paroxetine and did not breast-feed their infants, and 27 mothers who breast fed their infants but did not take any drugs. Participants completed a detailed outcome questionnaire at 3 months to 1 year after the birth of their child. Additional infant data were obtained from specific follow-up forms routinely completed by the paediatricians and nurses at well baby clinics and paediatric services in Israel. Infant weight and developmental milestones at ages 3, 6, and 12 months were recorded. There were no statistically significant differences between the paroxetine group and control groups in mean infant weight at ages 6 and 12 months. The usual developmental milestones were reached in all groups. There were no reported adverse effects of paroxetine during lactation except for irritability in one infant. Mothers expressed satisfaction with the treatment. CONCLUSION: paroxetine use during breast-feeding does not affect infant weight gain and rarely has adverse effects on the infant. Paroxetine may be an acceptable solution for depression in lactating women provided that they adhere to four important restrictions: use lowest dose (20 mg/day), preferable single bed-time dose, avoid combinations of drugs, and ensure close medical follow-up of the infant.

[Vitamin B6 (Pyridoxine)--excessive dosage in food supplements and OTC medications].

Vitamin B6 (Pyridoxine) is sold in Israel as a supplement and is available over-the-counter (OTC) without regulation. High intake of this vitamin is found in patients with premenstrual syndrome, carpal tunnel syndrome, pregnancy associated nausea and vomiting, decreasing homocysteine levels and improving cognitive function. Mega-doses of this vitamin may result in intoxication. In this review we will outline vitamin B6 function, daily recommended intake, deficiency signs and patients in deficiency risk, and the clinical spectrum of vitamin B6 intoxication.

Is immunosuppression therapy in renal allograft recipients teratogenic? A single-center experience.

The aim of the study was to determine whether immunosuppressive agents used in renal allograft recipients are teratogenic or otherwise associated with pregnancy outcome. The study population consisted of 38 renal allograft recipients treated with combinations of prednisone, azathioprine, cyclosporin A, and tacrolimus attending our Hypertension in Pregnancy Clinic. The 48 live offspring of 73 pregnancies in this group were evaluated for major congenital malformations and mild errors of morphogenesis. Findings were compared with those in 48 offspring of 41 women with primary renal disease not treated with immunosuppressive drugs. Pregnancy outcome parameters were also compared between the study and control groups in the perinatal period and on a long-term basis (2-7 years after birth). Two major anomalies (4.2%), subcoronal hypospadias and rudimentary thumb, and 10 mild errors of morphogenesis (20.8%) were detected in the study group. These rates did not differ significantly from those in the control group (4.2% and 16.6%, respectively). Pregnancy outcome was worse in the renal transplant patients than in the women with primary renal disease in terms of prematurity (60% vs. 21%, P = 0.001), growth restriction (52% vs. 17%, P = 0.001), and hospitalization in a neonatal intensive care unit (35% vs. 6%, P = 0.01). In conclusion, the similar prevalence of major anomalies and mild errors of morphogenesis in offspring of the renal transplant patients and the women with primary renal disease suggests that immunosuppressive therapy is not a teratogenic factor. It may, however, be associated with worse pregnancy outcome.

Oral antihyperglycemic agents during pregnancy and lactation: a review.

The treatment approach of diabetes mellitus during pregnancy requires a combination of diet, exercise, multiple home glucose determinations and intensive insulin regimens. During the last decade there was an increased interest in the use of oral antihyperglycemic agents (OAHAs) as an alternative to insulin in achieving good glycemic control. OAHAs are divided into four groups: derivatives of sulfonylurea, biguanides, glucosidase inhibitors and thiazolidinediones. This review describes the possible teratogenic effects of the use of OAHAs during pregnancy and the effects of these drugs during lactation. Animal and human studies assessing the teratogenic effects of OAHAs have yielded conflicting data because the risk of major malformations in infants of mothers with diabetes appears to be related to maternal glycemic control rather than the antidiabetic therapy. A major concern with the use of OAHAs during pregnancy is neonatal hypoglycemia, which may be severe and persist for days. Therefore, insulin is still the drug of choice because it has not been implicated as a teratogen in human pregnancies. In addition, because of the lack of data regarding the use of OAHAs in pregnancy, we cannot draw firm conclusions about all of the available drugs. However, OAHAs, especially glibenclamide (glyburide), may be beneficial in a situation where the proper use of insulin is problematic. Because there are very limited clinical data on the exposure of OAHAs to the infant via breast milk, and the potentially serious effect of neonatal hypoglycemia, the safest recommendation is not to breast feed while taking OAHAs. Well-conducted, prospective, controlled studies regarding the feasibility of OAHAs in pregnant women with diabetes and during lactation are needed.