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Background: Postpartum affective disorders may be associated with dysregulation of gonadal steroids. We investigated peripheral levels of allopregnanolone and progesterone in a combined group of women with postpartum onset of severe depression and/or psychosis who, as previously reported, responded with rapid symptom remission during sublingual estradiol treatment. The aim was to assess differences in allopregnanolone and progesterone between patients and healthy controls at baseline, and hormonal changes during estradiol treatment and symptom remission in patients.

Methods: Allopregnanolone and progesterone in serum were analyzed with radioimmunoassay before and four weeks after initiation of sublingual estradiol treatment in ten women with postpartum depression and four women with postpartum psychosis (ICD-10). Twenty-eight healthy postpartum controls were included for baseline comparison.

Results: Allopregnanolone declined significantly during estradiol treatment while there was a trend for lower baseline allopregnanolone levels in patients compared with healthy postpartum controls. The ratio between allopregnanolone and progesterone was significantly lower in patients compared with controls and it remained unchanged after clinical recovery.

Limitations: This study is a secondary analysis of two estradiol treatment studies based on availability of samples for the analysis of allopregnanolone. Healthy controls were assessed earlier after delivery. Data on potential confounders (somatic health, breastfeeding, other medication) were not available.

Conclusions: These preliminary findings suggest that clinical recovery of severe postpartum depression and psychosis during estradiol treatment does not seem to depend on increasing levels of allopregnanolone. Differences in progesterone metabolism may constitute a risk factor for severe postnatal affective dysregulation.

Objective: To assess the effect of lateral episiotomy, compared with no episiotomy, on obstetric anal sphincter injury in nulliparous women requiring vacuum extraction. Design: A multicentre, open label, randomised controlled trial.

Setting: Eight hospitals in Sweden, 2017-23.

Participants: 717 nulliparous women with a single live fetus of 34 gestational weeks or more, requiring vacuum extraction were randomly assigned (1:1) to lateral episiotomy or no episiotomy using sealed opaque envelopes. Randomisation was stratified by study site.

Intervention: A standardised lateral episiotomy was performed during the vacuum extraction, at crowning of the fetal head, starting 1-3 cm from the posterior fourchette, at a 60° (45-80°) angle from the midline, and 4 cm (3-5 cm) long. The comparison was no episiotomy unless considered indispensable.

Main outcome measures: The primary outcome of the episiotomy in vacuum assisted delivery (EVA) trial was obstetric anal sphincter injury, clinically diagnosed by combined visual inspection and digital rectal and vaginal examination. The primary analysis used a modified intention-to-treat population that included all consenting women with attempted or successful vacuum extraction. As a result of an interim analysis at significance level P<0.01, the primary endpoint was tested at 4% significance level with accompanying 96% confidence interval (CI).

Results: From 1 July 2017 to 15 February 2023, 717 women were randomly assigned: 354 (49%) to lateral episiotomy and 363 (51%) to no episiotomy. Before vacuum extraction attempt, one woman withdrew consent and 14 had a spontaneous birth, leaving 702 for the primary analysis. In the intervention group, 21 (6%) of 344 women sustained obstetric anal sphincter injury, compared with 47 (13%) of 358 women in the comparison group (P=0.002). The risk difference was -7.0% (96% CI -11.7% to -2.5%). The risk ratio adjusted for site was 0.47 (96% CI 0.23 to 0.97) and unadjusted risk ratio was 0.46 (0.28 to 0.78). No significant differences were noted between groups in postpartum pain, blood loss, neonatal outcomes, or total adverse events, but the intervention group had more wound infections and dehiscence.

Conclusions: Lateral episiotomy can be recommended for nulliparous women requiring vacuum extraction to significantly reduce the risk of obstetric anal sphincter injury. Trial registration: ClinicalTrials.gov NCT02643108.

Context: Adrenal insufficiency (AI) is usually diagnosed by low plasma cortisol levels following a short Synacthen test (SST). Most plasma cortisol is bound to corticosteroid-binding globulin, which is increased by estrogen in combined estrogen-progestin oral contraceptives (COCs). Women with AI using COCs are therefore at risk of having an apparently normal plasma cortisol level during SST, which would not adequately reflect AI.

Objective: To test whether salivary cortisol or cortisone during SST is more robust against the COC effect and to calculate the lower reference limits (LRLs) for these to be used as tentative diagnostic cutoffs to exclude AI.

Methods: Forty-one healthy women on COCs and 46 healthy women without exogenous estrogens performed an SST with collection of plasma and salivary samples at 0, 30, and 60 min after Synacthen injection. The groups were compared using regression analysis with age as covariate and the LRLs were calculated parametrically.

Results: SST-stimulated plasma cortisol levels were significantly higher in the COC group versus controls, while mean salivary cortisol and cortisone levels were slightly lower in the COC group. Importantly, COC use did not significantly alter LRLs for salivary cortisol or cortisone. The smallest LRL difference between groups was seen for salivary cortisone.

Conclusion: Salivary cortisol and especially salivary cortisone are considerably less affected by COC use than plasma cortisol during SST. Due to similar LRLs, a common cutoff for salivary cortisol and cortisone during SST can be used to exclude AI in premenopausal women irrespective of COC use.

In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3-8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum, and circulating levels are reflected in the brain. Allopregnanolone is a modulator of the GABA(A) receptor, enhancing the effect of gamma-aminobutyric acid (GABA). Previous studies have demonstrated different sensitivity to other GABA(A) receptor agonists, i.e., benzodiazepines, alcohol, and pregnanolone, in PMDD patients compared to controls.

This study aimed to investigate the sensitivity to intravenous allopregnanolone over the menstrual cycle in PMDD patients.

Allopregnanolone, 0.05 mg/kg, was administered intravenously once in the mid-follicular and once in the luteal phase of the menstrual cycle to 10 PMDD patients and 10 control subjects. The saccadic eye velocity (SEV) was recorded by electrooculography as a measurement of functional GABA(A) receptor activity, at baseline and repeatedly after the injection. A mixed model was used to analyze data.

There was a highly significant group x phase interaction in the SEV response to allopregnanolone (F(1,327.489) = 12.747, p < 0.001). In the PMDD group, the SEV response was decreased in the follicular phase compared to the luteal phase (F(1,168) = 7.776, p = 0.006), whereas in the control group, the difference was opposite during the menstrual cycle (F(1,158.45) = 5.70, p = 0.018).

The effect of exogenous allopregnanolone is associated with menstrual cycle phase in PMDD patients and in controls. The results suggest an altered sensitivity to allopregnanolone in PMDD patients.

Background: One of the major complications related to delivery is labor dystocia, or an arrested labor progress. Many dystocic deliveries end vaginally after administration of oxytocin, but a large numbers of women with labor dystocia will undergo a long and unsafe parturition. As a result of the exertion required in labor, the uterus produces lactate. The uterine production of lactate is mirrored by the level of lactate in amniotic fluid (AFL). Objectives: To evaluate whether the level of AFL, analysed in a sample of amniotic fluid collected vaginally at arrested labor when oxytocin was needed, could predict labor outcome in nulliparous deliveries. Methods: A prospective multicentre study including 3000 healthy primiparous women all with a singleton pregnancy, gestational age 37 to 42 weeks and no maternal/fetal chronic and/or pregnancy-related conditions. A spontaneous onset of labor, regular contractions and cervical dilation >= 3 cm were required before the women were invited to take part in the study. Results: AFL, analysed within 30 minutes before augmentation, provides information about delivery outcome. Sensitivity for an acute cesarean section according to high (>= 10.1 mmol/l) or low (< 10.1mmol/l) AFL values was 39.0% (95% CI; 27-50), specificity 90.3% (95% CI; 87-93) PPV 37.3% (95% CI; 27-48) and NPV was 91.0% (95% CI; 88-93). The overall percentage of correct predictions of delivery outcome when the AFL level was used was 83.7%. Deliveries with a high AFL-level correlated with delivery time > 12h (p = 0.04), post-partum fever (> 38 degrees C, p = 0.01) and post-partum haemorrhage > 1.5L (p = 0.04). Conclusion: The AFL is a good predictor of delivery outcome in arrested nulliparous deliveries. Low levels of AFL may support the decision to continue a prolonged vaginal labor by augmentation with oxytocin. A high level of AFL correlates with operative interventions and post-partum complications.

ObjectiveTo assess whether the frequency of adverse neonatal outcome at delivery is related to the level of lactate in amniotic fluid and to the use of oxytocin. DesignProspective observational study. SettingSoder Hospital, Stockholm, Sweden. PopulationSeventy-four women in active labor with a gestational age 36weeks and mixed parity. MethodsLevels of lactate in amniotic fluid were analyzed bedside from an intrauterine catheter every 30min during labor. Deliveries were divided into groups with and without oxytocin. Main outcome measuresThe frequency of adverse neonatal outcome at delivery. ResultOf the deliveries 13.5% (10/74) concluded with an adverse neonatal outcome. The levels of lactate in amniotic fluid increased during labor, more so in deliveries where oxytocin was used. In the group with an adverse neonatal outcome, the level of lactate in amniotic fluid was significantly higher in the final sample before delivery (p=0.04). In 18 deliveries, stimulation with oxytocin was temporarily halted for at least 30min due to overly stimulated labor contractions. A decreasing level of lactate in amniotic fluid was shown within a median 5%/30min. In the group where the administration of oxytocin was halted, there was no adverse neonatal outcome. ConclusionThe frequency of adverse neonatal outcome was associated with the level of lactate in amniotic fluid and with the use of oxytocin. The level of lactate in amniotic fluid may be an additional valuable tool when oxytocin is administered during labor.

Objective: Human deliveries commonly occur during the dark period of the day. Melatonin hormone is released as a circadian signal from the human brain, and has been shown to have a synergistic effect together with oxytocin in facilitating the uterine contractions during labor. Melatonin is inhibited by light and energized by dark. During winter the numbers of light hours per day in Sweden are few, but during the summer they are numerous. In Tanzania there is no season difference.

Study Design: In 2011,452 Tanzanian and 919 Swedish healthy primiparas with a normal pregnancy and a spontaneous onset of labor were included in the study. Time and date together with the length and outcome of delivery were studied, and a statistical comparison was made.

Results: 47% of the Swedish deliveries started in early morning, and 48% ended at midnight. The median time of active labor was significantly longer during the summer season (May to August vs. November to February, p=0.05). The frequency of labor dystocia was increased during summer season, and significantly more in the region on Sweden with midnight sun (29 vs. 40%, p=0.03).

48% of Tanzania labors started at midnight, and 41% ended at lunch time. Among Tanzanian women, no difference in median time of active delivery (p=0.5) or the frequency of dystocic labors was shown, according to season of the year (13.7 vs. 14.1 %, p=0.8).

Oxytocin was used in 68% of the Swedish deliveries, and the use was higher during the summer season. Oxytocin was used in 31% of the Tanzanian deliveries. No difference in use of oxytocin was shown according to season.

Conclusion: In this project a variation of labor dystocia according to season of the year has been studied. A significant overrepresentation of prolonged and dystocic deliveries were shown during the summer season in Sweden. This new knowledge may be of a great importance, when handling a dysfunctional labor.

OBJECTIVE: To examine whether binding of [3H]paroxetine to the platelet serotonin transporter or binding of [3H]lysergic acid diethylamide (LSD) to the platelet 5-HT(2A) receptor are influenced by postmenopausal estrogen/progestogen treatment. METHODS: Twenty-three postmenopausal women with climacteric symptoms completed this double-blind, randomized, crossover study. The women received 2 mg of estradiol continuously during four 28-day cycles. In the last 14 days of each cycle, 10 mg of medroxyprogesterone acetate, 1 mg of norethindrone acetate, or placebo was given. Before treatment, as well as once during the last week of each treatment, blood samples were collected for analysis of [3H]LSD and [3H]paroxetine binding. The power of the study setup was 81%. The study had an effect size of 0.36, corresponding to the ability to detect a 15% difference in [3H]paroxetine and [3H]LSD binding between treatments with alpha =.05 and beta =.20, based on a previously reported standard deviation within cells of 20% of the mean binding values. RESULTS: The number of platelet receptors (B(max)), or the affinity of the radioligand to the receptor (K(d)), for [3H]paroxetine binding did not change during estrogen or estrogen-progestogen treatment, nor did B(max) or K(d) for [3H]LSD binding change during the different treatments. However, in a subgroup of depressed patients, the decrease in B(max) for [3H]LSD binding during treatment was significantly more pronounced than in the nondepressed subgroup (P <.05). CONCLUSION: Estrogen treatment with or without the addition of progestogen does not affect binding to the serotonin transporter or to the serotonergic 5-HT(2A) receptor in healthy postmenopausal women.