Journal Article Annotations
2021, 1st Quarter

Women’s Mental Health

Annotations by Mary Burke, MD and Liliya Gershengoren, MD
March, 2021

Parental ADHD in pregnancy and the postpartum period – A systematic reviews.
Clinical Characteristics and outcomes in pregnant women with COVID-19 and the risk of vertical transmission: a systematic review.
Ulipristal Acetate for Treatment of Premenstrual Dysphoric Disorder: A Proof-of-Concept Randomized Controlled Trial.

PUBLICATION #1 — Women’s Mental Health

Parental ADHD in pregnancy and the postpartum period – A systematic review.

Kittel-Schneider S, Quednow BB, Leutritz AL, McNeill RV, Reif A

Abstract: Neurosci Biobehav Rev. 2021 May;124:63-77. doi: 10.1016/j.neubiorev.2021.01.002. Epub 2021 Jan 28.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders worldwide, and in the majority of patients persists into adulthood. However, it remains unclear how maternal ADHD could affect pregnancy and birth as well as early mother-(father)-child interaction. There are several studies investigating the effect of depressed or anxious parents on parent-child-interactions in early infancy, but data about the influence of parental ADHD is lacking although it is a common mental disorder in parents. Additionally, the prescription of stimulant and other ADHD medication for adult ADHD patients is rising due to improved diagnostic procedures and a greater awareness of this disorder in adulthood among psychiatrists and psychologists. However, this leads to increased numbers of treated ADHD women that wish to have children or experience unplanned pregnancies while taking stimulant medication. In our systematic review we aimed at analysing the current evidence for the association of maternal ADHD with pregnancy and birth outcomes, pregnancy risks and health behaviour in pregnancy, as well as the association of parental ADHD with early parent-child interaction and early child development in the first 3 years. Furthermore, we reviewed recent evidence on the risks of stimulant and non-stimulant treatment for ADHD in pregnancy and lactation.

Annotation

The finding:
Mothers with ADHD appear to have a higher risk of pregnancy and birth complications including pre-eclampsia, infection and caesarean section. Their infants are more likely to be treated in intensive care units. Based on their literature review, the authors suggest that amphetamines add no risk for congenital malformations and likely little risk for placental dysfunction while methylphenidate might have some risk for cardiovascular malformations, placental dysfunction, and perinatal complications. The authors note that it is uncertain whether the aforementioned associations are the result of methylphenidate use or the maternal ADHD itself. It was also highlighted that there is a higher risk of unplanned as well as teenage pregnancies for those with ADHD.

Strength and weaknesses:
There are very few studies that explore parents with ADHD and its impact during the perinatal period and early infancy of their offspring. This study is a systematic review focusing on ADHD of the parents in the perinatal period. The aim was to investigate existing evidence for the association between maternal ADHD and pregnancy/birth outcomes in addition to the parent-child interaction in the early infancy. However, the authors identified a need for more studies in this area including sibling designs and exploration of possible confounders.

Relevance:
C-L psychiatrists working in obstetrical settings will encounter women with ADHD and will be asked to consider inquiries regarding the implications of ADHD and ADHD medication during the perinatal period and beyond.

Type of study:
Systematic review or meta-analysis

PUBLICATION #2 — Women’s Mental Health

Clinical Characteristics and outcomes in pregnant women with COVID-19 and the risk of vertical transmission: a systematic review.

Jianhua Chi, Wenjian Gong, Qinglei Gao

Abstract: Arch Gynecol Obstet. 2021 Feb;303(2):337-345. doi: 10.1007/s00404-020-05889-5. Epub 2020 Dec 1.

Purpose:
This systematic review summarizes the clinical features and maternal–infant outcomes of 230 pregnant women (154 patients gave birth) infected with COVID-19 and their 156 infants, including the possibility and evidence of vertical transmission.

Methods:
An electronic search of PubMed, Embase, Medline, MedRxiv, CNKI, and the Chinese Medical Journal Full Text Database following PRISMA guidelines was performed through April 18, 2020. Search terms included COVID-19, SARSCoV- 2, pregnant women, infants, and vertical transmission.

Results:
A total of 230 women with COVID-19 (154 deliveries, 66 ongoing pregnancies, and 10 abortions) and 156 newborns from 20 eligible studies were included in this systematic review. A total of 34.62% of the pregnant patients had obstetric complications, and 59.05% of patients displayed fever. Lymphopenia was observed in 40.71% of patients. A total of 5.19% of women received mechanical ventilation. Seven women were critically ill. One mother and two newborns died. A total of 24.74% of newborns were premature. Five newborns’ throat swab tests of SARS-CoV-2 were positive, all of which were delivered by cesarean section. For eight newborns with negative throat swab tests, three had both elevated IgM and IgG against SARS-CoV-2. Nucleic acid tests of vaginal secretions, breast milk, amniotic fluid, placental blood, and placental tissues were negative.

Conclusion:
Most pregnant patients were mildly ill. The mortality of pregnant women with COVID-19 was lower than that of overall COVID-19 patients. Cesarean section was more common than vaginal delivery for pregnant women with COVID-19. Premature delivery was the main adverse event for newborns. The vertical transmission rate calculated by SARS-CoV-2 nucleic acid tests was 3.91%. Serum antibodies against SARS-CoV-2 should be tested more frequently, and multiple samples should be included in pathogenic testing.

Keywords:
COVID-19 · Delivery · Infants · Pregnancy · SARS-CoV-2 · Vertical transmission

Annotation

The finding:
The clinical manifestations of COVID-19 in pregnant women are similar to the general population. Maternal mortality among infected women (0.43%) was similar to women worldwide. 25% of infected women had chronic diseases such as diabetes. The rate of overall obstetrical complications was 35%. Rate of vertical transmission to the baby is low, but elevated levels of infant IgG and IgM suggest rare fetal infection. The authors also note that 5 women chose to have abortions for fear of the effects of the virus on the fetus, although fetal negative outcomes were rare, with prematurity being the most common.

Strength and weaknesses:
This was an important, early, and comprehensive survey of maternal-fetal outcomes by two physicians from Wuhan, using six databases in both English and Chinese. The authors used PRISMA guidelines.

Relevance:
CL psychiatrists working with obstetrical teams should be informed about the impact of the SARS-CoV2 virus on their patients

Type of study:
Systematic review or meta-analysis

PUBLICATION #3 — Women’s Mental Health

Ulipristal Acetate for Treatment of Premenstrual Dysphoric Disorder: A Proof-of-Concept Randomized Controlled Trial.

Erika Comasco, Helena Kopp Kallner, Marie Bixo, Angelica L Hirschberg, Sara Nyback, Haro de Grauw, C Neill Epperson, Inger Sundström-Poromaa

Abstract: Am J Psychiatry. 2021 Mar 1;178(3):256-265. doi: 10.1176/appi.ajp.2020.20030286. Epub 2020 Dec 10.

Objective:
Premenstrual dysphoric disorder (PMDD) is a common mood disorder, characterized by distressing affective, behavioral, and somatic symptoms in the late luteal phase of the menstrual cycle. The authors investigated continuous treatment with a selective progesterone receptor modulator, ulipristal acetate (UPA), as a potential treatment for PMDD.

Methods:
The authors conducted an investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial in which women with PMDD (N=95) were treated with either 5 mg/day of UPA or placebo during three 28-day treatment cycles. The primary outcome was the change in premenstrual total score on the Daily Record of Severity of Problems (DRSP) from baseline to end of treatment. DRSP scores were captured by daily ratings using a smartphone application and were analyzed with linear mixed models for repeated measures.

Results:
The mean improvement in DRSP score after 3 months was 41% (SD=18) in the UPA group, compared with22% (SD=27) in the placebo group (mean difference 218%; 95% CI=229, 28). Treatment effects were also noted for the DRSP depressive symptom subscale (42% [SD=22] compared with 22% [SD=32]) and the DRSP anger/irritability subscale (47% [SD=21] compared with 23% [SD=35]), but not for the DRSP physical symptom subscale. Remission based on DRSP score was attained by 20 women in the UPA group (50.0%) and eight women in the placebo group (21.1%) (a statistically significant difference).

Conclusions:
If these results are replicated, UPA could be a useful treatment for PMDD, particularly for the psychological symptoms associated with the disorder.

Annotation

The finding:
Ulipristal, a progesterone-blocker used to treat uterine fibroids, was effective in a blinded, randomized trial, at reducing symptoms of PMDD. Patients receiving ulipristal had better mean improvement in Daily Record of Severity of Problems (DRSP) score (41% improvement) compared to patients receiving placebo (22%). Remission based on DRSP score was 50% among ulipristal patients versus 21% among women receiving placebo.

Strength and weaknesses:
This was a double-blinded, parallel-group, multi-center trial. Since the treatment can cause amenorrhea, some patients were aware of their assignments and unblinded. Many of the authors have pharmaceutical ties although ulipristal is also sold generically. In Europe, ulipristal is recommended for restricted use only due to risk of liver failure.

Relevance:
PMDD can be truly debilitating and SSRI’s—often the first line medication—are not always effective. There was significant symptom reduction in this study, and a statistically significant number needed to treat of 3. Ulipristal may be an option for PMDD treatment, although long-term risks of liver failure need to be clarified for how long this medication can be safely used.

Type of study:
Randomized controlled trial