Pregnancy adapted ICBT for antenatal depression is feasible, acceptable and efficacious. These results need to be replicated in larger trials to validate these promising findings.

Aim: Antiepileptic drugs (AEDs) are known teratogens. Some specificity between different AEDs has been noted in the literature. The aim was to compare the teratogenic effect of valproic acid (VPA) and carbamazepine (CBZ) in monotherapy. Methods: Infants exposed to AEDs (n= 1398) in early pregnancy were identified from the Swedish Medical Birth Registry. The number of infants with congenital malformations and exposed to AED was compared with the expected number estimated from all infants born (n= 582656). Results: 90% (1256) of the AED exposed children were exposed to AEDs in monotherapy, 56% were exposed to CBZ and 21% to VPA. The odds ratio (OR) for having a malformation in the AED exposed group was 1.86 [95% confidence interval (95% CI) 1.42‐2.44]. Exposure to VPA in monotherapy compared with CBZ in monotherapy gave OR = 2.51 (95% CI 1.43‐4.68) for a neonatal diagnosis of malformations. However, there is no information available on the number of therapeutic abortions, or the different types of epilepsy or drug dosage in the two treatment groups. Conclusion: There was a small increase in the risk of having a major malformation after exposure to AEDs in monotherapy. Exposure to VPA seems to carry a higher risk than exposure to CBZ.

The distal 3p deletion syndrome is characterized by developmental delay, low birth weight and growth retardation, micro- and brachycephaly, ptosis, long philtrum, micrognathia, and low set ears. We have used FISH and BACs in order to map three 3p deletions in detail at the molecular level. The deletions were 10.2-11 Mb in size and encompassed 47-51 known genes, including the VHL gene. One of the deletions was interstitial, with an intact 3p telomere. In nine previously published patients with 3p deletions, the size of the deletion was estimated using molecular or molecular cytogenetic techniques. The genotype, including genes of interest, and the phenotype of these cases are compared and discussed. The localization of the proximal breakpoint in one of our patients suggests that the previously identified critical region for heart defects may be narrowed down, now containing three candidate genes. We can also conclude that deletion of the gene ATP2B2 alone is not enough to cause hearing impairment, which is frequently found in patients with 3p deletion. This is the third reported case with an interstitial deletion of distal 3p.

To estimate the rate of admissions to NICUs, as well as infants' morbidity and neonatal interventions, after exposure to antidepressant drugs in utero.METHODS: Data on pregnancies, deliveries, prescription drug use, and health status of the newborn infants were obtained from the Swedish Medical Birth Register, the Prescribed Drug Register, and the Swedish Neonatal Quality Register. We included 741 040 singletons, born between July 1, 2006, and December 31, 2012. Of the infants, 17 736 (2.4%) had mothers who used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Infants exposed to an SSRI were compared with nonexposed infants, and infants exposed during late pregnancy were compared with those exposed during early pregnancy only. The results were analyzed with logistic regression analysis. RESULTS:After maternal use of an SSRI, 13.7% of the infants were admitted to the NICU compared with 8.2% in the population (adjusted odds ratio: 1.5 [95% confidence interval: 1.4-1.5]). The admission rate to the NICU after treatment during late pregnancy was 16.5% compared with 10.8% after treatment during early pregnancy only (adjusted odds ratio: 1.6 [95% confidence interval: 1.5-1.8]). Respiratory and central nervous system disorders and hypoglycemia were more common after maternal use of an SSRI. Infants exposed to SSRIs in late pregnancy compared with early pregnancy had a higher risk of persistent pulmonary hypertension (number needed to harm: 285).CONCLUSIONS: Maternal use of antidepressants during pregnancy was associated with increased neonatal morbidity and a higher rate of admissions to the NICU. The absolute risk for severe disease was low, however.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• CYP3A4 converts cholesterol into 4b-hydroxycholesterol.• We have suggested that 4b-hydroxycholesterol could be used as a clinical marker for CYP3A4 activity aiding in dose adjustments.• The kinetics of 4b-hydroxycholesterol formation is not known, however, and must be determined in order to establish under what conditions 4b-hydroxycholesterol can be used as a CYP3A marker. WHAT THIS STUDY ADDS• The concentration of 4b-hydroxycholesterol increases very slowly during CYP3A4/5 induction in paediatric patients.• Whereas induction of CYP3A4/5 was apparently complete within 1-2 weeks of carbamazepine treatment, plasma 4b-hydroxycholesterol levels continued to increase until at least 8 weeks of treatment. AIMSTo investigate the time course of the increase in 4b-hydroxycholesterol and carbamazepine plasma concentrations during treatment of paediatric patients with epilepsy. METHODSEight paediatric patients with newly diagnosed epilepsy were studied. Blood samples were drawn before and after about 1, 2, 4, 8 and 16 weeks of carbamazepine treatment. The plasma concentrations of 4b-hydroxycholesterol were determined by gas chromatography-mass spectrometry and carbamazepine and its epoxide metabolite by high-performance liquid chromatography. RESULTSThe basal plasma concentrations of 4b-hydroxycholesterol showed a large range of observed values between 18 and 99 ng ml . Plasma concentrations of carbamazepine and its epoxide metabolite reached steady state at 1-2 weeks after last dose change. CONCLUSIONSCarbamazepine treatment of paediatric patients with epilepsy resulted in an induction of CYP3A4/5 and a concomitant increase in plasma 4b-hydroxycholesterol. Whereas the induction of CYP3A4/5 was apparently complete after 1-2 weeks, the increase in 4b-hydroxycholesterol continued for several weeks. Thus CYP3A4 activity is not the only determinant of the circulating level of 4b-hydroxycholesterol. Additional factors such as transport and storage or presence of another enzyme may thus be of importance.

The subtle delay in locomotor development evaluated with the Griffiths' test at 4.5-5 y of age in children exposed to phenytoin may indicate a subtle influence on psychomotor development, which may be more obvious at school age: thus, larger studies and further follow-up are warranted.

The study demonstrates a slightly increased risk only for preeclampsia, vaginal hemorrhage after delivery, and respiratory distress in the newborn after the use of AEDs during pregnancy.

BackgroundIntrauterine exposure to antidepressants may lead to neonatal symptoms from the central nervous system, respiratory system and gastrointestinal system. Finnegan score (Neonatal Abstinence Score, NAS) has routinely been used to assess infants exposed to antidepressants in utero.AimThe purpose was to study neonatal maladaptation syndrome in infants exposed to selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI) in utero.MethodRetrospective cohort study of women using antidepressants during pregnancy and their infants. Patients were identified from the electronic health record system at Karolinska University Hospital Huddinge containing pre-, peri- and postnatal information. Information was collected on maternal and infant health, social factors and pregnancy. NAS sheets were scrutinized.Results220 women with reported 3rd trimester exposure to SSRIs or SNRIs and who gave birth between January 2007 and June 2009 were included. Seventy seven women (35%) used citalopram, 76 used (35%) sertraline, 34 (15%) fluoxetine and 33 (15%) other SSRI/SNRI. Twenty-nine infants (13%) were admitted to the neonatal ward, 19 were born prematurely. NAS was analyzed in 205 patients. Severe abstinence was defined as eight points or higher on at least two occasions (on a scale with maximum 40 points), mild abstinence as 4 points or higher on at least two occasions. Seven infants expressed signs of severe abstinence and 46 (22%) had mild abstinence symptoms. Hypoglycemia (plasma glucose <2.6 mmol/L) was found in 42 infants (19%).ConclusionSevere abstinence in infants prenatally exposed to antidepressants was found to be rare (3%) in this study population, a slightly lower prevalence than reported in previous studies. Neonatal hypoglycemia in infants prenatally exposed to antidepressant may however be more common than previously described.