Objective

Prior studies have shown an increased vulnerability among males, to adverse outcomes during the postnatal period. The majority of children exposed to opioids and other medication in utero develop a neonatal abstinence syndrome (NAS), yet individual predisposition for NAS is poorly understood. This investigation examines the role of neonatal sex in the postnatal period, for neonates exposed to standardized opioid maintenance treatment in utero with a focus on the neonatal abstinence syndrome (NAS) regarding severity, medication requirements and duration.

Patients and Methods

This is a secondary analysis of data collected in a prospective randomized, double-blind, double-dummy multi-center trial examining the comparative safety and efficacy of methadone and buprenorphine during pregnancy (Maternal Opioid Treatment: Human Experimental research MOTHER – study). 131 neonates born to opioid-dependent women randomized at six US sites (n=74) and one European site (n=37) were analyzed. Sex-based differences in birth weight, length, head circumference, NAS duration, NAS severity, and treatment parameters of full-term neonates were assessed.

Results

Males had a significantly higher birth weight (p=0.027) and head circumference (p=0.017) than females, with no significant sex difference in rates of preterm delivery. No significant sex-related differences were found for NAS development, severity, duration, or medication administered with non significant differences in concomitant drug consumption during pregnancy (p =0.959).

Conclusions

This unique prospective study shows similar postnatal vulnerability for both sexes, suggesting that factors other than sex are the major determinants of clinically significant NAS.

Aims

To investigate whether cigarette smoking and/or depression contribute to neonatal abstinence syndrome (NAS) severity.

Design

Cohort study analyzing data from a randomized, controlled trial of methadone versus buprenorphine.

Setting

Seven study sites that randomized patients to study conditions and provided comprehensive addiction treatment to pregnant patients.

Participants

119 of 131 opioid-dependent pregnant patients who completed the MOTHER study.

Measurements

Smoking data and depression status were obtained from the Addiction Severity Index and Mini International Neuropsychiatric Interview, respectively. Neonatal outcomes (birth weight, preterm delivery and NAS pharmacologic treatment) were collected from the medical charts. Study site was a fixed-effect factor in all analyses.

Findings

Cigarette smoking was reported by 94% of participants and depression identified in 35%. Smoking was associated with low birth weight, preterm delivery, and NAS pharmacologic treatment in both depressed and non-depressed participants. The association between smoking and NAS treatment differed significantly between depressed and non-depressed participants. Among non-depressed participants, adjusting for site and illicit drug use, each additional average cigarette per day (CPD) increased the odds of NAS treatment by 12% [95%CI: (1.02-1.23), p=0.02]. Among depressed participants, each additional average CPD did not statistically increase the odds of NAS treatment [OR: 0.94, 95% CI: (0.84-1.04), p=0.23].

Conclusions

These results are consistent with the hypothesis that NAS expression is influenced by many factors. The relationship between CPD and NAS pharmacologic treatment is attenuated among depressed women in this study for reasons currently unknown. Further investigations are needed to clarify the complex relationships among maternal smoking, depression, and NAS.

Gender, a biological determinant of mental health and illness, plays a critical role in determining patients’ susceptibility, exposure to mental health risks, and related outcomes. Regarding sex differences in the epidemiology of opioid dependence, one third of the patients are women of childbearing age. Women have an earlier age of initiation of substance use and a more rapid progression to drug involvement and dependence than men. Generally few studies exist which focus on the special needs of women in opioid maintenance therapy. The aim of this paper is to provide an overview of treatment options for opioid-dependent women, with a special focus on buprenorphine, and to look at recent findings related to other factors that should be taken into consideration in optimizing the treatment of opioid-dependent women. Issues addressed include the role of gender in the choice of medication assisted treatment, sex differences in pharmacodynamics and pharmacokinetics of buprenorphine drug interactions, cardiac interactions, induction of buprenorphine in pregnant patients, the neonatal abstinence syndrome and breastfeeding. This paper aims to heighten the awareness for the need to take gender into consideration when making treatment decisions in an effort to optimize services and enhance the quality of life of women suffering from substance abuse.

The comorbidity of schizophrenia and substance abuse has attracted increasing attention in the past years, with multiple potential links, including genetic vulnerability, neurobiological aspects, side effects of medications, and psychosocial factors being under discussion. The link between the use of substances and the development of psychoses is demonstrated by the high prevalence of substance abuse in schizophrenia. Apart from alcohol misuse, substances commonly abused in this patient group include nicotine, cocaine, and cannabis. In particular, heavy cannabis abuse has been reported to be a stressor eliciting relapse in schizophrenic patients. In general, substance use in psychosis is associated with poorer outcomes, including increased psychotic symptoms and poorer treatment compliance. Since both disorders have been observed to be closely interdependent, a particular treatment for schizophrenic patients with comorbidity of substance abuse is needed in order to provide more effective care. In this article, we discuss various potential modes of interaction and interdependence, and the possibility of embarking on new therapeutic paths for treating this particular population.