Use of antidepressants during pregnancy in the Netherlands: observational study into postpartum interventions

We conducted an observational study in a teaching hospital in Amsterdam, the Netherlands. The psychiatric, obstetric, pediatric clinic of this hospital is a center of expertise for pregnancy and psychiatric disorders and advises women with a psychiatric disorder before, during and after pregnancy. Primary care givers (mainly general practitioners, midwifes, obstetricians and psychiatrists) refer patients to this clinic. Approximately 50% of all women who visit this clinic live in the catchment area and deliver in our hospital. In case of home birth, or birth in another hospital due to capacity problems in our hospital, within 8hours postpartum these women are admitted to the maternity ward, together with their infants.

During hospital admission, nurses, pediatricians, obstetricians and psychiatrists observe, evaluate, support and treat mother and infant for 72 h. The psychiatrist evaluates possible psychiatric symptoms in mothers and adjusts the psychotropic medication if necessary (changes the dosage or type of psychotropic medication or starts additional medication). The psychiatrist uses the hospital anxiety and depression scale (HADS), which is a validated questionnaire for symptoms of anxiety and depression and is completed at the first day postpartum delivery [20, 21]. If psychiatric care after hospital discharge is too limited or in case social problems, such as absence of a support system, are detected external organizations can be consulted. The obstetrician assesses the physical condition of the mother and treats complications if necessary. Infants are physically examined by the pediatrician and treated in case of pathology. Trained nurses assess poor neonatal adaptation in infants with use of the Finnegan scoring list three times a day [22]. This observational tool is used to monitor the moment of onset and development of symptoms of poor neonatal adaptation. A Finnegan score of four or higher is an indication for poor neonatal adaptation [3, 5, 12]. The pediatrician determines if PNA has been present or absent, based on the Finnegan scores and physical examination and observation. In case of indistinctness about the origin of symptoms, additional testing can be necessary to exclude other neonatal pathology, such as perinatal infection [3, 5, 13, 14]. When poor neonatal adaptation has been diagnosed supportive measures such as swaddling are mostly sufficient. Infants with severe poor neonatal adaptation (multiple Finnegan scores of ≥ 8 and severe symptoms such as convulsions) are admitted to the neonatal care unit and can be treated with phenobarbital. Parents are supported by explanation and reassurance. Furthermore, the team observes the mother-infant interaction. If interaction difficulties are present external organizations can be consulted to provide family care.

Exclusion criteria were use of illicit drugs [23] or regular alcohol use of more than two units per week during last trimester of pregnancy, admission to the psychiatric department up to delivery and postpartum transfer to another hospital. In order to create mother-infant dyads, in case of multiple pregnancies one infant was randomly selected.

Mother-infant dyads were analyzed for medical interventions that had been performed during hospital admission, all caused by exposure to selective antidepressants or the maternal psychiatric disorder. These interventions were: 1. adjustment of psychotropic medication 2. admission to the psychiatric department 3. additional investigations due to indistinctness about the origin of neonatal symptoms whereby the final diagnose was poor neonatal adaptation. 4. treatment of poor neonatal adaptation and 5. consultation of an external organization for additional family care. The prevalence of interventions was established by calculating the percentage of mother-infant dyads in which one or more interventions were performed. All base-line characteristics were compared between mother-infant dyads in which an intervention was performed and dyads whereby no intervention was performed.

For the first four interventions the time to intervention (hours postpartum) was analyzed. For the fifth intervention (consultation of an external organization for additional family care) time was not analyzed because organizations are generally contacted at hospital discharge.

Per mother-infant dyad the time to the final intervention was investigated. This was exclusively done for dyads in which times of all interventions were known.

The time to intervention was divided into <12 h, 13–24, 25–48, 49–72 and >72 h postpartum. The time to the intervention ‘treatment of poor neonatal adaptation’ was defined as the moment of administration of pharmacotherapy or the moment of the first Finnegan score of four or higher in case of supportive treatment. The time to other interventions was established by the time noted in the patient files of mother and infant.

In order to examine if there are factors which are associated with late time of intervention, all base-line characteristics were compared between mother-infant dyads in which the final intervention was performed within 48 h and dyads in which the final intervention was performed after 48 h postpartum.

Data were analyzed by SPSS version 21 (IBM, New York, USA). In all continuous variables, the mean and standard deviation were presented in case of a normal distribution. Otherwise, the median and inter quartile range were presented. The base-line characteristics of mother-infant dyads in which an intervention was performed were compared to the characteristics of dyads in which no intervention was performed. Continuous, normally distributed variables were compared with the independent sample t test. Continuous, skewed variables were compared with the Mann Whitney U test. Dichotomous or categorical variables were compared with the chi square test. In case more than 20% of the expected cell counts were less than five the Fisher exact test was performed. A result was considered statistically significant if the p-value was not larger than 0.05. The base-line characteristics of dyads in which the final intervention was performed within or after 48 h were compared in the same manner. In addition, odds ratios (OR) and 95% confidence intervals (CI) were estimated using univariate analysis.

In the period of January 1st 2007 till December 31st 2012, a total of 330 mothers who used selective antidepressants during at least the last trimester of pregnancy were admitted to the maternity ward of our hospital for observation. Two mothers delivered a twin, one of each twin was randomly excluded. One mother-infant dyad was excluded because the mother used soft drugs during pregnancy and five dyads were excluded because they were transferred to another hospital. In three dyads this transfer was based on severe medical problems, which were fluxus, neonatal breathing difficulties and neonatal asphyxia. In the end, 324 mother-infant dyads (98.2%) were included (Fig. 1). Of these mothers, 304 mothers (93.8%) delivered in our hospital, 13 mothers (4.0%) delivered at home and 7 mothers (2.2%) delivered in another hospital. The maternal and neonatal characteristics are presented in Table 1. Three mothers (0.9%) decided to go home before medical discharge, all after at least 48 h of observation. Of the 324 mothers, 310 (95.7%) were known with an affective disorder, some in combination with other psychiatric disorders. Of the 291 mothers who solely used an antidepressant, 209 used an selective serotonin reuptake inhibitors, 32 a serotonin norepinephrine reuptake inhibitors, 35 a noradrenergic and specific serotonergic antidepressants and 1 a norepinephrine-dopamine reuptake inhibitor. Fourteen mothers used a combination of antidepressants. See Appendix for an overview of antidepressants used in our study population.

Of the 324 mother-infant dyads, a total of 143 dyads (61.1%) needed one or more intervention. One intervention was performed in 70.6% of dyads. In 24.5% two and in 4.9% three or four interventions were performed.

In 76 mothers (23.5%) the psychotropic medication was adjusted. The main reasons were symptoms of depression or anxiety and sleeping difficulties. No mothers had to be admitted to the psychiatric department. Nine infants (2.8%) underwent additional tests due to indistinctness about the origin of neonatal symptoms. Additional testing, which included blood tests, brain ultrasounds, a chest radiograph and electroencephalography excluded other pathology where after poor neonatal adaptation was diagnosed in all nine infants. The pediatrician diagnosed poor neonatal adaptation in 76 infants (23.5%). These infants showed mild symptoms of sleeping- as well as feeding difficulties, tremors and jitteriness. One infant was treated with phenobarbital as these symptoms of restlessness were more severe and prolonged. All other infants were treated with supportive measures. External support was organized for eight mother-infant dyads (2.5%), which consisted of psychiatric home care, social welfare and support regarding infant development.

The time to interventions are presented in Fig. 2. In 63 of the 143 dyads in which an intervention was performed, the time of at least one intervention was unknown. Thus, we analyzed time to the final intervention in 80 mother-infant dyads. In 67.5% of these dyads one intervention was performed and in 32.5% multiple interventions were performed. In 6 of the dyads (7.5%), the final intervention was performed within 12 h, in 28 (35%) between 13 and 24 h, in 26 (32.5%) between 25 and 48 h, in 16 (20.0%) between 49 and 72 and in 4 (5.0%) after 72 h postpartum.

Base-line characteristics were compared between mother-infant dyads in which the final intervention was performed within 48 h and dyads in which the final intervention was performed after 48 h postpartum (Table 2). This revealed no statistically significant differences.