Koert M. Dolman

Antidepressants during pregnancy and postpartum hemorrhage: a systematic review.

The use of antidepressants in pregnancy is increasing. Concerns have risen about the use of antidepressants during pregnancy and the risk of postpartum hemorrhage (PPH). The aim of this systematic review is to summarize evidence on the association between use of antidepressants during pregnancy and the risk of PPH. An Embase and Pubmed search was conducted. English and Dutch language studies reporting original data regarding bleeding after delivery associated with exposure to antidepressants during pregnancy were selected. Quality appraisal was conducted using the Newcastle Ottawa Scale (NOS). Out of 81 citations, 4 studies were included. Based on the NOS, 3 were considered of good quality and 1 was considered of satisfactory quality. Two studies reported an increased incidence of PPH in women who used antidepressants during pregnancy. The other two studies identified no overall increased risk of PPH among pregnant women exposed to antidepressants. The existing evidence remains inconclusive whether use of antidepressants during pregnancy is associated with an increased risk of postpartum hemorrhage. If there is such an association the absolute increased risk will be low and the clinical relevance needs to be further examined.

Risk factors for poor neonatal adaptation after exposure to antidepressants in utero

Infants exposed to antidepressants in utero are at risk of developing poor neonatal adaptation (PNA). This study identified risk factors for PNA.

Mirtazapine in pregnancy and lactation - A systematic review.

Depression is common in pregnancy and associated with increased risk of adverse effects for the neonate. Treatment and prevention options include antidepressant therapy. The aim of this paper was to review the literature on safety of mirtazapine during pregnancy and lactation. In 31 papers a total of 390 cases of neonates exposed to mirtazapine during pregnancy or lactation have been described. There might be an association between mirtazapine and spontaneous abortion, however, this might be attributable to underlying psychiatric disease. An increased risk of major neonatal malformations associated with mirtazapine in pregnancy has not been reported. Although one study showed a nearly significant increase in occurrence of respiratory problems and hypoglycaemia, no indication of causality could be given. No other significant adverse effects on neonates were reported. Limited available data, four papers on 11 exposed neonates, suggest that use of mirtazapine during breastfeeding is safe due to a low relative infant dose. High plasma levels might be associated with increased body weight and sleep. However, the reported data are too scarce to come to a clear assessment of the risk of mirtazapine in lactation. No information is available on the use of mirtazapine in pregnancy and Poor Neonatal Adaptation Syndrome (PNAS) or neurobehavioral development at an age over one year. In conclusion, mirtazapine seems to be safe in pregnancy, especially regarding incidence of congenital malformations. There are not enough data available to come to a conclusion on the safety of mirtazapine during lactation.

Adapted Finnegan scoring list for observation of anti-depressant exposed infants

Abstract Objective: The Finnegan scoring list (FSL) is widely used to screen for poor neonatal adaptation in infants exposed to anti-depressants in utero. However, the large number of FSL-items and differential weighing of each item is time consuming. The aim of this study was to shorten and simplify the FSL yet preserving its clinimetric properties. Methods: This observational study examined infants exposed to an anti-depressant during pregnancy admitted for at least 72 h on a maternity ward. Trained nurses completed the FSL three times daily. Items for the adapted FSL were selected through forward analysis whereby the number of selected items was based on the area under the curve (AUC). Internal validity was assessed by cross-validation. Results: 183 infants met the inclusion criteria. By forward analysis eight equally-weighed items resulted in an AUC of 0.91. In cross-validation, the mean AUC was 0.89 for 8 items. This adapted FSL had a sensitivity of 97.7% and specificity of 37.0% and a sensitivity of 41.9% and specificity of 86.2% regarding a cut-off of, respectively, 1 and 2. Conclusions: An adapted FSL with eight equally-weighed items has acceptable clinimetric properties and can serve as an easy to apply screening tool in infants exposed to anti-depressants during pregnancy.

Mirtazapine in pregnancy and lactation: data from a case series.

Abstract Depression is a common disorder in pregnancy and associated with adverse effects for both mother and neonate. Pharmacological treatment and prevention options include mirtazapine. In a series of 56 cases, we investigated neonatal outcome after intrauterine exposure to mirtazapine and exposure through lactation in the first days postpartum. No increase in any neonatal complication was observed. None of the infants exposed to mirtazapine in the first trimester were born with a major malformation. Of the 54 infants exposed to mirtazapine in the third trimester, 14 were diagnosed with poor neonatal adaptation syndrome (PNAS). This incidence (25.9%) is similar to the incidence of PNAS after intrauterine exposure to other antidepressants. The incidence of PNAS after exposure to mirtazapine was significantly diminished in children who were partially or fully breastfed (18.6% versus 54.5%, P = 0.024).

Serotonin and poor neonatal adaptation after antidepressant exposure in utero.

Objective Infants exposed to selective antidepressants (SADs) in utero are at risk to develop poor neonatal adaptation (PNA) postpartum. As symptoms are non-specific and the aetiology of PNA is unknown, the diagnostic process is hampered. We hypothesised that the serotonin metabolism plays a role in the aetiology of PNA. Methods In this controlled study, infants admitted postpartum from February 2012 to August 2013 were included and followed for 3 days. Infants exposed to SADs during at least the last 2 weeks of fetal life were included in the patient group (n=63). Infants not exposed to psychotropic medication and admitted postpartum for another reason were included in the control group (n=126). The neonatal urinary 5-hydroxyindoleacetid acid (5-HIAA) levels of SAD-exposed infants who developed PNA, SAD-exposed infants who did not develop PNA and control infants were compared. Results The course of the 5-HIAA levels over the first 3 days postpartum differed between infants with and without PNA (p≤0.001) with higher 5-HIAA levels in infants with PNA on day 1 (2.42 mmol/mol, p=0.001). Presence of maternal psychological distress modified this relationship. Conclusions A transient disturbance of the neonatal serotonergic system may play a role in the aetiology of PNA. Other factors, including the presence of maternal psychological distress, also seem to play a role.

Is poor neonatal adaptation after exposure to antidepressant medication related to fetal cortisol levels? An explorative study

BACKGROUND As a marker for poor neonatal adaptation (PNA) is lacking, the diagnostic process is difficult and includes invasive additional testing. AIMS In order to develop a marker, it is essential to gain insight into the etiology of PNA. We hypothesized that the fetal cortisol level may play a role in this etiology. STUDY DESIGN Non-randomized, prospective controlled study. OUTCOME MEASURES We examined hair cortisol levels of infants exposed and not exposed to selective antidepressants (SADs) during pregnancy. These cortisol levels represent the mean cortisol level during the last trimester of pregnancy. Infants exposed to SADs who developed PNA according to the pediatrician (PNA+, n=25), infants exposed to SADs who did not develop PNA (PNA-, n=40) and infants not exposed to SADs (controls, n=105) were compared. RESULTS In infants with PNA, hair cortisol levels were higher compared to infants without PNA. However this difference was only statistically significant in female infants (girls B0.33, p=0.04, boys B0.05, p=0.82). There was no correlation between nonspecific distress, measured by the Finnegan score and fetal hair cortisol levels (B-0.15, p=0.30). All analyses were adjusted for type of delivery and gestational age. CONCLUSIONS Our results suggest that the hypothalamic pituitary adrenal (HPA) axis activity may play a sex-specific role in the development of PNA. As PNA is most likely of a multifactorial origin, it would be interesting to examine other factors possibly involved in the etiology of PNA in future studies, such as (epi) genetics.