Prolactin in Pregnancies Affected by Pre-Existing Maternal Metabolic Conditions: A Systematic Review.

Women affected by maternal pregestational diabetes mellitus (type 1 or type 2) or by polycystic ovary syndrome experience an increased risk of pregnancy complications, as well as suboptimal lactation outcomes. The hormone prolactin plays important roles in pregnancy and postpartum, both as a metabolic and lactogenic hormone. We aimed to explore, through a systematic review, the relationship between pregestational maternal metabolic conditions and prolactin levels in pregnancy and postpartum. MEDLINE via OVID, CINAHL Plus, and Embase were searched from inception to 9 May 2022. Eligible studies included women who were pregnant or up to 12 months postpartum and had a pre-existing diagnosis of type 1 or type 2 diabetes mellitus or polycystic ovary syndrome; with reporting of at least one endogenous maternal serum prolactin level during this time. Two independent reviewers extracted the data. Eleven studies met the eligibility criteria. The studies were too diverse and heterogeneous to enable meta-analysis. Overall, prolactin levels appeared to be lower in pregnancies affected by type 1 diabetes mellitus. There was little data in polycystic ovary syndrome or type 2 diabetes pregnancy, but prolactin increment across pregnancy in polycystic ovary syndrome emerged as an area for future study. During postpartum, lactation difficulties in women with metabolic disease present before pregnancy are well-described, but the relationship to prolactin remains unclear. Overall, preliminary evidence suggests that pre-existing maternal metabolic disease may alter prolactin dynamics in pregnancy and postpartum. Further well-designed studies in modern cohorts, with standardised collection and serial sampling across pregnancy and postpartum, are required to clarify these associations.

Human Placental Lactogen in Relation to Maternal Metabolic Health and Fetal Outcomes: A Systematic Review and Meta-Analysis.

Human placental lactogen (hPL) is a placental hormone which appears to have key metabolic functions in pregnancy. Preclinical studies have putatively linked hPL to maternal and fetal outcomes, yet-despite human observational data spanning several decades-evidence on the role and importance of this hormone remains disparate and conflicting. We aimed to explore (via systematic review and meta-analysis) the relationship between hPL levels, maternal pre-existing and gestational metabolic conditions, and fetal growth. MEDLINE via OVID, CINAHL plus, and Embase were searched from inception through 9 May 2022. Eligible studies included women who were pregnant or up to 12 months post-partum, and reported at least one endogenous maternal serum hPL level during pregnancy in relation to pre-specified metabolic outcomes. Two independent reviewers extracted data. Meta-analysis was conducted where possible; for other outcomes narrative synthesis was performed. 35 studies met eligibility criteria. No relationship was noted between hPL and gestational diabetes status. In type 1 diabetes mellitus, hPL levels appeared lower in early pregnancy (possibly reflecting delayed placental development) and higher in late pregnancy (possibly reflecting increased placental mass). Limited data were found in other pre-existing metabolic conditions. Levels of hPL appear to be positively related to placental mass and infant birthweight in pregnancies affected by maternal diabetes. The relationship between hPL, a purported pregnancy metabolic hormone, and maternal metabolism in human pregnancy is complex and remains unclear. This antenatal biomarker may offer value, but future studies in well-defined contemporary populations are required.

Prolactin in relation to gestational diabetes and metabolic risk in pregnancy and postpartum: A systematic review and meta-analysis.

Context: Pre-clinical evidence suggests that prolactin has important metabolic functions in pregnancy and postpartum, in addition to lactogenic actions. Objective: To explore the relationship between prolactin and maternal metabolic outcomes in human pregnancy and postpartum, particularly in relation to gestational diabetes mellitus (GDM). Data sources: MEDLINE via OVID, CINAHL plus, Embase. Study selection: Eligible studies included women who were pregnant or up to 12 months postpartum, reporting at least one maternal serum prolactin level in relation to key metabolic outcomes including GDM, glycaemic parameters, obesity, and gestational weight gain. Data extraction: Two independent reviewers extracted data. Data synthesis: Twenty-six articles were included. Meta-analysis showed no relationship between maternal prolactin levels and GDM status, with a weighted mean difference of -2.14 ng/mL (95% CI -12.54 to 8.27 ng/mL, p=0.7) between GDM and controls in early pregnancy (n=3 studies) and -3.89 ng/mL (95% CI, -15.20 to 7.41 ng/mL, p=0.5) in late pregnancy (n=11 studies). In narrative synthesis of other outcomes (due to study heterogeneity and/or lack of data), prolactin levels were not associated with maternal glycaemic or weight-related parameters during pregnancy, but in the postpartum period (particularly with lactation) a high-prolactin environment was associated with low circulating insulin and beta-cell function, and increased insulin sensitivity. Conclusions: Current evidence from human studies does not clearly support a relationship between prolactin and metabolic parameters during pregnancy, including with GDM status. Elevated prolactin was associated with lower insulin and beta-cell function and higher insulin sensitivity in the post-partum period, but the direction of causality remains unclear. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42021262771].

Lactogenic hormones in relation to maternal metabolic health in pregnancy and postpartum: protocol for a systematic review.

INTRODUCTION: Maternal metabolic disease states (such as gestational and pregestational diabetes and maternal obesity) are reaching epidemic proportions worldwide and are associated with adverse maternal and fetal outcomes. Despite this, their aetiology remains incompletely understood. Lactogenic hormones, namely, human placental lactogen (hPL) and prolactin (PRL), play often overlooked roles in maternal metabolism and glucose homeostasis during pregnancy and (in the case of PRL) postpartum, and have clinical potential from a diagnostic and therapeutic perspective. This paper presents a protocol for a systematic review which will synthesise the available scientific evidence linking these two hormones to maternal and fetal metabolic conditions/outcomes. METHODS AND ANALYSIS: MEDLINE (via OVID), CINAHL and Embase will be systematically searched for all original observational and interventional research articles, published prior to 8 July 2021, linking hPL and/or PRL levels (in pregnancy and/or up to 12 months postpartum) to key maternal metabolic conditions/outcomes (including pre-existing and gestational diabetes, markers of glucose/insulin metabolism, postpartum glucose status, weight change, obesity and polycystic ovary syndrome). Relevant fetal outcomes (birth weight and placental mass, macrosomia and growth restriction) will also be included. Two reviewers will assess articles for eligibility according to prespecified selection criteria, followed by full-text review, quality appraisal and data extraction. Where possible, meta-analysis will be performed; otherwise, a narrative synthesis of findings will be presented. ETHICS AND DISSEMINATION: Formal ethical approval is not required as no primary data will be collected. The results will be published in a peer-reviewed journal and presented at conference meetings, and will be used to inform future research directions. PROSPERO REGISTRATION NUMBER: CRD42021262771.

Prevalence and Risk Factors of Premature Ovarian Insufficiency/Early Menopause.

Premature ovarian insufficiency (POI) and early menopause, defined as loss of ovarian activity prior to 40 years or menopause between the ages of 40 and 45 years, respectively, is associated with significant adverse health impacts. Recent data indicate that the prevalence of POI and early menopause is greater than was previously thought, affecting more than 10% of women. Biopsychosocial risk factors including genetic, autoimmune, reproductive, lifestyle, early-life, social/environmental, and iatrogenic have been associated with POI/early menopause or earlier age at menopause. However, establishing a causal role and the underlying mechanisms remains elusive. Understanding and clarification of these risk factors will facilitate prevention and risk minimization strategies to optimize women's health.

SGLT2 Inhibitors Increase the Risk of Diabetic Ketoacidosis Developing in the Community and During Hospital Admission.

CONTEXT: Diabetic ketoacidosis (DKA) has been associated with the use of sodium glucose cotransporter 2 inhibitors (SGLT2is). OBJECTIVE: To determine the incidence, characteristics, and outcomes of DKA in SGLT2i users vs nonusers with type 2 diabetes. DESIGN: Retrospective, multicenter, controlled cohort study. SETTING: All public hospitals in Melbourne and Geelong (combined population of 5 million), Australia, from 1 September 2015 to 31 October 2017. PATIENTS: Consecutive cases of DKA that developed in the community, or during the course of hospital admission, in patients with type 2 diabetes. MAIN OUTCOME MEASURES: In SGLT2i users vs nonusers: (i) OR of DKA developing during hospital admission, and (ii) incidence of DKA. RESULTS: There were 162 cases of DKA (37 SGLT2i users and 125 non-SGLT2i users) with a physician-adjudicated diagnosis of type 2 diabetes. Of these, DKA developed during the course of inpatient admission in 14 (38%) SGLT2i users vs 2 (2%) non-SGLT2i users (OR, 37.4; 95% CI, 8.0 to 175.9; P < 0.0001). The incidence of DKA was 1.02 per 1000 (95% CI, 0.74 to 1.41 per 1000) in SGLT2i users vs 0.69 per 1000 (95% CI, 0.58 to 0.82 per 1000) in non-SGLT2i users (OR, 1.48; 95% CI, 1.02 to 2.15; P = 0.037). Fifteen SGLT2i users (41%) had peak blood glucose <250 mg/dL (14 mmol/L) compared with one (0.8%) non-SGLT2i user (P < 0.001). CONCLUSIONS: SGLT2i users were more likely to develop DKA as an inpatient compared with non-SGLT2i users. SGLT2i use was associated with a small but significant increased risk of DKA.

Evolving epidemiology of injecting drug use-associated infective endocarditis: A regional centre experience.

INTRODUCTION AND AIMS: Injecting drug use (IDU) is a major risk factor for infective endocarditis (IE). An understanding of the epidemiology of IE and IDU is vital for delivery of health care for this disease. Our aim was to examine the rates of IDU-associated IE (IDU-IE) in a single centre over the last 12 years. DESIGN AND METHODS: Retrospective analysis of two cohorts of consecutive patients (n = 226) admitted with IE from 2002 to 2013. Numbers of cases and rates of IE were compared between two cohorts (2002-2006 and 2009-2013). Rate ratios were calculated using Poisson distributions. Poisson regression was used to examine relationship over time. RESULTS: One hundred thirty cases of endocarditis were seen in the first observation period (6 IDU-IE) and 96 in the second observation period (15 IDU-IE). The estimated incidence rate of IE had fallen from 10.1 to 6.45 per 100, 000 person-years [rate ratio 0.64, 95% confidence interval (CI) 0.48, 0.85]. In contrast, the estimated incidence rate of IDU-E has risen from 0.48 to 0.79 per 100, 000 person-years (rate ratio 1.65, 95% CI 0.59, 4.57). Incidence rate regression suggests that the number of IDU-IE cases is expected to increase by a factor of 1.25 (95%CI 1.09-1.44) for each increase of 1 year. DISCUSSION AND CONCLUSIONS: Over the last decade, there has been a decrease in incidence rate and total number of cases of IE but a rise in rate and number of cases of IDU-IE. This may indicate increasing IDU or increased rates of endocarditis in intravenous drug users in this region. This finding may inform health-care planning in the area.