WITHDRAWN: Hypospadias induced by medications and environmental exposures- A scoping review.

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Use of Cannabis in Fetal Alcohol Spectrum Disorder.

Background: Fetal alcohol spectrum disorder (FASD) has been recently estimated to afflict up to 5% of American children. Most of these children exhibit different degrees of symptomatology of disruptive behaviors. Yet, there has been very little research on the efficacy and safety of pharmacological modalities, limited mostly to stimulants for attention deficit hyperactive disorder or second generation atypical antipsychotics for aggression. Recently, the use of cannabinoids has been described for symptoms related to autistic spectrum disorder with apparent favorable effects, as well as for other disruptive behaviors. The objective of our study was to follow up in a retrospective case series the effect of cannabis in children and young adults diagnosed with FASD. Methods: In two children and three FASD young adults with severe disruptive behavior, changes in behavior after cannabis use were measured by the parent version of the Nisonger Child Behavior Rating Form. Results: In all five cases, there was a highly statistical decrease in the disruptive behavior score from 18±1.0 before cannabis use to 6±2.1 after introduction of cannabis (p=0.0002). Discussion: In children and young adults with FASD, cannabis, mostly cannabidiol (CBD), has been associated with a marked and statistically significant improvement in serious disruptive behavior. These cases suggest that the efficacy and safety of CBD should be tested in well-controlled studies.

Measuring the severity of nausea and vomiting of pregnancy; a 20-year perspective on the use of the pregnancy-unique quantification of emesis (PUQE).

Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting up to 80% of expectant women. Measuring the severity of the condition over time is important for management decisions, as well as for research into different therapeutic modalities. Twenty years ago we described and validated the Pregnancy Unique Quantification of Emesis scale (PUQE), as a clinical and research tool. PUQE has become widely used for both ends, and has been incorporated in numerous practice guidelines worldwide. In this review we describe the inception of the tool, its rational, and its wide range of use worldwide.

Medicinal Use of Cannabis in Children and Pregnant Women.

The increasing medicinal use of cannabis during recent years has largely overlooked children and pregnant women due to litigious and ethical concerns. However, over the last few years medicine has observed increasing numbers of children treated with cannabis for autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD), and pregnant women treated for hyperemesis gravidarum (HG). This review provides an account of major findings discovered through this research. Specifically, cannabis may offer therapeutic advantages to behavioral symptoms of autism spectrum disorder and fetal alcohol spectrum disorder, and to the severe nausea and vomiting in hyperemesis gravidarum. The use of medical cannabis in children and pregnant women should be further discussed and researched in this patient population.

The use of cannabis for Hyperemesis Gravidarum (HG).

BACKGROUND: Hyperemesis Gravidarum (HG) responds only partially to standard antiemetic medications. Cannabis has been known to possess antiemetic effects and there are several medicinal cannabinoids used as anti -emetics for cancer chemotherapy. Its favorable use for HG has been described in social media, but not in the medical literature. METHODS: We evaluated 4 women with HG counseled by the Motherisk Program, before and following the use of cannabis. Using the validated Pregnancy Unique Quantification of Emesis (PUQE) scoring system and employing the Student's paired t test, we compared changes in symptoms following initiation of cannabis. RESULTS: There was a highly significant improvement in symptoms: PUQE score improved from 14.5+/- 1 to 7.5+/- 0.58(p = 0.0004). Cannabis use was associated with a significant increase in the PUQE Quality of Life scale, from 2+/- 0.82 to 7+/- 0.82 (p = 0.0012). CONCLUSIONS: The results suggest that cannabis may be effective for HG, and should be studied in appropriately powered, controlled studies, fully considering potential fetal risks.

Quantifying fetal alcohol exposure by meconium fatty acid ethyl esters (FAEE); association with adverse fetal outcomes and population estimates of fetal alcohol exposure.

Fetal Alcohol Spectrum Disorder (FASD) describes the wide range of adverse physical, behavioral and cognitive effects resulting from ethanol exposure during embryonic and fetal development. Identification of children suffering from FASD is often difficult, as abuse of ethanol during pregnancy is a heavily stigmatized behavior that receives little prenatal screening attention in routine care. Over the last 3 decades, measurement of the ethanol metabolites fatty acid ethyl esters (FAEE) has emerged as a useful tool to detect in the neonatal period fetal alcohol exposure starting from mid gestation. This review aims at updating clinicians and researchers on the validity and utility of this biological marker in two aspects: The association with adverse fetal outcomes and in generating population estimates of fetal alcohol exposure.

[FETAL ALCOHOL SPECTRUM DISORDER (FASD) AND ADOPTIONS FROM THE FORMER SOVIET UNION].

INTRODUCTION: Fetal alcohol spectrum disorder is presently estimated to affect more than 1-2 % of babies in North America. In Israel it is quite rarely diagnosed. Many of the children adopted from the former Soviet Union were born to alcoholic women. BACKGROUND: A 4.5 year old boy adopted from Ukraine, presented with inattention, hyperactivity and aggressiveness. He was born with severe intra uterine growth restriction (IUGR) and continued to grow on the 3rd percentile. His biological mother was alcohol dependent. DISCUSSION: This case highlights the need to consider the differential diagnosis of children with ADHD plus aggressive behavior, as well as maintaining a high index of suspicion of FASD in children adopted from the Soviet Union.

[PR-EMPTIVE TREATMENT FOR HYPEREMESIS GRAVIDARUM].

BACKGROUND: Hyperemesis gravidarum (HG) affects around 1% of pregnant women. The experience is traumatic, and many women hesitate to start a subsequent pregnancy in view of the tendency of HG to re-occur. OBJECTIVES: A 25 year old woman who experienced HG in her previous pregnancy was very afraid to start a second pregnancy, as she considered the termination of the first, traumatic pregnancy. She was advised to use pre- emptive antiemetic therapy with an anti emetic drug before any symptom appeared. The pregnancy passed with only mild nausea and vomiting. DISCUSSION: Several controlled randomized studies have shown the effectiveness of pre emptive therapy in preventing a repeat of HG symptoms.

Correction: Chronic use of psychotropic medications in breastfeeding women: Is it safe?

[This corrects the article DOI: 10.1371/journal.pone.0197196.].

Chronic use of psychotropic medications in breastfeeding women: Is it safe?

BACKGROUND: Current knowledge regarding chronic use of psychotropic medications during breastfeeding is limited. The objective of this study was to evaluate the long-term effects of psychotropic monotherapy use during lactation on the breastfed infant. MATERIALS AND METHODS: In this prospective study, we followed 280 infants whose mothers contacted the Drug Consultation Center (DCC) at Assaf Harofeh Medical Center between January 2011 and December 2015, seeking information regarding the chronic use of psychotropic medications during lactation. This group was compared with a group of 152 callers, who inquired evidence regarding the use of antibiotics compatible with breastfeeding. Information on adverse effects, physical measures and gross motor developmental milestone achievements of the breastfed infants was obtained during a follow-up telephone interview. At follow up, the median age of the infants in the Psychotropic-drug group was 20 (11-33) months versus 36 (20-48) months in the Antibiotic group (p < 0.001). The outcomes were compared between the groups followed by a propensity score matching to control for difference in baseline characteristics. RESULTS: At follow-up, no significant differences between infants in the two groups were observed with regard to height, weight, head circumference and weight-length ratio percentile (p = 0.339, p = 0.223, p = 0.738, p = 0.926, respectively). Children in both groups were, according to their parents, within the normal developmental range for all milestones, according to the Denver Developmental Scale. Use of psychotropic medications during breastfeeding was not significantly associated with adverse reactions. After propensity score matching (n = 120 pairs) to control for differences in baseline characteristics and the length of lactation, only one significant difference was reported, sleepiness in infants in the study group (7/120) and none in the comparison group (p = 0.008). CONCLUSIONS: Chronic use of psychotropic monotherapy during lactation is associated with normal growth and gross motor developmental as by milestone achievements reported by parents. Sleepiness was reported, it seemed self-limited with no developmental effect.

Safety of Mebendazole Use During Lactation: A Case Series Report.

INTRODUCTION: Mebendazole is an effective drug widely used in the treatment of parasitic infections. Although theoretically considered as safe during lactation, no studies have evaluated its potential adverse effects in infants of breastfeeding mothers. OBJECTIVES: We aimed to evaluate the safety of mebendazole in infants of lactating women treated with the drug. METHODS: Women referred for consultation regarding mebendazole use were invited to participate in the study. Overall 45 lactating women treated with various protocols of mebendazole were recruited in this case series study. RESULTS: Regardless of the treatment protocol used (single or repeated doses) mebendazole was well tolerated and was not associated with any adverse effects in infants of lactating mothers. There was mild GI irritability in two treated women. CONCLUSION: This study provides first evidence in humans as to the safety of mebendazole in breastfeeding.

[THE APPROACH TO NAUSEA AND VOMITING IN PREGNANCY].

Nausea and vomiting of pregnancy (NVP) is the most prevalent medical condition during gestation. Approximately 85% of pregnant women suffer from some degree of this condition, while hyperemesis gravidarum (HG), the most severe form, affects up to 2% of women. Although being the leading cause for hospitalization during pregnancy, NVP has received little attention from the medical community. NVP negatively affects women's quality of life, household activity and work productivity. In Canada, the financial cost of NVP, ranges from $132 to $653 per woman/week. In extreme cases, severe NVP results in therapeutic abortions. On the other hand, NVP has been shown to have a protective effect against spontaneous abortions and congenital malformations. Lately, there has been an interest in the hypothesis that NVP is a mechanism protecting the fetus from phytochemicals. Early treatment can prevent future complications and deterioration of the symptoms. Various studies have demonstrated the effectiveness and safety of antiemetic therapy in pregnancy. However, fear of teratogenicity and lack of clinical guidelines lead to trial and error NVP management. We present an updated algorithm for the management of NVP.

Intestinal obstruction in pregnancy by ondansetron.

BACKGROUND: Ondansetron use for nausea and vomiting during pregnancy has increased in the last years, although its maternal and fetal safety is not conclusive. CASE: We describe a case of intestinal obstruction in a pregnant woman with severe nausea and vomiting of pregnancy treated with ondansetron, which is known to slow gut motility. CONCLUSION: The spontaneous reporting system of WHO confirms that this potentially life threatening complication is more common than what the peer review literature may suggest and needs to be looked into carefully, especially in view of the wide spread off-label use for NVP.