Gestational diabetes mellitus, pre-eclampsia and future cardiovascular disease: need to consider both BMI and gestational weight gain to investigate the linkLionel Carbillon1, 3, Amélie Benbara1, Emmanuel Cosson2, 31Department of Obstetrics and Gynecology, Paris-Seine Saint Denis University Hospitals, Assistance Publique – Hopitaux de Paris, Paris 13 University, France2 Department of Endocrinology, Diabetology, Nutrition, Paris-Seine Saint Denis University Hospitals, Assistance Publique – Hôpitaux de Paris, France3Sorbonne North Paris University
Exposure to extreme heat in pregnancy increases the risk of stillbirth. Progress in reducing stillbirth rates has stalled, and populations are increasingly exposed to high temperatures and climate events that may further undermine health strategies. This narrative review summaries the current clinical and epidemiological evidence of the impact of maternal heat exposure on stillbirth risk. 19 out of 20 studies found an association between heat and stillbirth risk. Recent studies based in low- middle- income countries and tropical settings add to the existing literature to demonstrate that all populations are at risk. Additionally, both short-term heat exposure and whole-pregnancy heat exposure increase the risk of stillbirth. A definitive threshold of effect has not been identified, as most studies define exposure as > 90 th percentile of the usual temperature for that population. Therefore, the association between heat and stillbirth has been found with exposures from as low as >12.64°C up to >46.4°C. The pathophysiological pathways by which maternal heat exposure may lead to stillbirth, based on human and animal studies, include both placental and embryonic or fetal impacts. Although evidence gaps remain and further research is needed to characterise these mechanistic pathways in more detail, preliminary evidence suggests epigenetic changes, alteration in imprinted genes, congenital abnormalities, reduction in placental blood flow, size and function all play a part. Finally, we explore this topic from a public health perspective; we discuss and evaluate the current public health guidance on minimising the risk of extreme heat in the community. There is limited pregnancy specific guidance within heatwave planning, and no evidence-based interventions have been established to prevent poor pregnancy outcomes. We highlight priority research questions to move forward in the field and specifically note the urgent need for evidence-based interventions that are sustainable.
Title Guideline consultation generates inevitable challenges but invaluable communication SignatoryPauline McDonagh Hull, Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Alberta, CanadaLetterDear Sir, As first author of one of the BJOG letters cited in Dr. Murphy’s commentary on the ‘unwelcome consequences of guideline authorship’1 (‘Montgomery is missing from RCOG’s Assisted Vaginal Birth guideline’),2 and director of one of the organisations that submitted comments during the Royal College of Obstetricians and Gynaecologists’ consultation, I would appreciate the opportunity to clarify my involvement and position in the matters described, to avoid potential misinterpretations or assumptions where individuals and organisations have not been named. Dr. Murphy mentions ‘individuals who…believe that forceps should be abolished entirely’, and informs readers this view ‘was reflected in one submission…from a patient advocacy organisation who suggested that planned caesarean section should be recommended to women as a means of avoiding AVB.’ She then notes that our Montgomery letter2 ‘repeated the same point about planned caesarean section they had made during the consultation process.’ For the record, the submission from my voluntary organisation, Caesarean Birth, did not suggest forceps should be abolished, and proposed offering, not recommending, planned caesareans. I disagree with Dr. Murphy’s assertion that our letter was ‘hostile’, and we stand by the concerns expressed therein. However, where I do agree with Dr. Murphy is in relation to the irrefutable challenge ‘of reconciling polarised views’. While our criticism of the RCOG guideline may be perceived as ‘an agenda’ to ‘undermine authors’, it may also be perceived as a sincere effort to influence a hegemonic shift in maternity services in the face of unprecedented maternity litigation resulting from avoidable harm. These views may never be fully reconciled, but I believe we all share the same goal of improving health outcomes. Moreover, the RCOG has responded to criticism of its assisted vaginal birth and caesarean birth recommendations in the past; initially removing them from its website temporarily, and then permanently, five years later.3Last year, the University of Aberdeen was awarded almost 1 million GBP to develop a novel decision aid, to be offered to all women, for planning mode of birth.4 In my view, the option of planned caesarean birth should not be reserved for obstetricians or women who initiate discussions, as this does not constitute equitable care. Language in maternity services is changing too. While Dr. Murphy refers to ‘caesarean section’, both the RCOG and National Institute for Health and Care Excellence (NICE) adopted ‘caesarean birth’ for their respective 2021 guideline and 2022 Considering a caesarean birth publications. Finally, when Dr. Murphy highlights the lack of remuneration for guideline authors, she echoes my own experience of countless hours in unpaid consultation; barring one significant difference. Only authors have the privilege of determining the final version. We also concur on the importance of providing stakeholders the opportunity for public debate. Prior to reading Dr. Murphy’s commentary, I was not aware of the complaint she received, and certainly support individual safeguarding as we all navigate the inevitable disagreements ahead. Nevertheless, open channels of communication and consultation remain a valuable and indispensable method to examine, and in some cases disrupt, established ways of thinking, and they must not be diminished.References1. Murphy DJ. The unwelcome consequences of Guideline authorship. BJOG 2023;00:1-2. 2. McDonagh Hull PM, Thomas K, Skinner E, Dawes A, Christensen P. Re: assisted vaginal birth: green-top guideline no. 26: Montgomery is missing from RCOG’s assisted vaginal birth guideline. BJOG2020;127(10):1297–8. 3. Weston N. Making sense of commissioning Maternity Services in England – some issues for Clinical Commissioning Groups to consider . Royal College of Obstetricians and Gynaecologists, 14 August 2012. 4. Scientists awarded £1million to help women make childbirth choices. University of Aberdeen, 27 September 2022. https://www.abdn.ac.uk/news/16386/. Accessed 5 June 2023.
Cause for optimism in mild hypoxic ischaemic hypoxic encephalopathyWilliam M. Curtin, MD, corresponding authorDivision of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology & Pathology and Laboratory Medicine, Penn State College of Medicine, Penn State Health, Milton S. Hershey Medical Center, Hershey, PA, USAwcurtin@pennstatehealth.psu.eduMail code H103500 University Dr, PO Box 850Hershey, PA 17033-0850Maternal-Fetal Medicine, Rm C3620Phone 717-531-8142/Option #5Fax 717-531-0947Acknowledgements: noneDisclosure of Interests: The author has no conflicts nor competing interests to disclose, financial or otherwise, in connection with this manuscript.Contribution to Authorship: Dr. Curtin alone completed review of the Törn et al. final manuscript entitled “Outcomes in children after mild neonatal hypoxic ischaemic encephalopathy: A population-based cohort study” The writings and opinions expressed in his mini commentary are solely the work of Dr. Curtin.Details of Ethics Approval: not applicable at our institution’s IRB as a commentary is not considered research and does not involve human subjects.Funding: Dr. Curtin neither received nor utilized any funds in writing this mini commentary.The objective of the study by Törn et al. was to determine if mild hypoxic ischaemic encephalopathy (HIE) was associated with severe neurological outcomes utilizing a population-based approach facilitated by five linked Swedish national databases. The rationale given was that while moderate to severe HIE is known to be associated with significant neurological morbidity, long-term disability, and mortality in children, less is known about mild HIE. The authors note that half of the cases of HIE are mild and they cite a systematic review of 250 infants (Conway JM, et al. Early human development . 2018; 120:80-7) showing a 22% prevalence of abnormal neurological outcomes in this disorder. There is therefore potential for significant burden of disease in mild HIE. Törn et al. chose a primary composite outcome that included cerebral palsy, epilepsy, mental retardation and death in children with mild HIE and non HIE cohorts followed up to 6 years of age. With a median follow-up of 3.3 years of age, 17 of 414 (4.1%) and 4786 of 504,661 (0.95%), in the mild HIE and non HIE cohorts respectively, had the composite outcome with an adjusted hazard ratio of 3.85 (95% CI: 2.27-6.50)In 1976 Sarnat and Sarnat reported clinical and EEG features of 21 neonates at term who experienced ischaemic-anoxic encephalopathy (Sarnat HB et al. Arch Neurol. 1976; 33:696–705). This temporal classification divided the infants into three progressively deteriorating stages. Fast forward to the current millennium and Sarnat’s original classification is used to differentiate between infants with mild and moderate/severe HIE, the latter two categories benefiting from therapeutic hypothermia (Jacobs SE et al. Cochrane Database Syst Rev. 2013, Issue 1. Art. No.: CD003311). Seven infants with moderate or severe HIE is the number needed to treat (NNT) to prevent one adverse neurological outcome.Therapeutic hypothermia is not standard of care in mild HIE; however, in a survey of neonatal clinicians from 35 countries the vast majority would support a large randomized controlled trial to examine neurodevelopmental outcomes (Singla M, et al. Neonatology. 2022; 119:712-718). The results from this methodical Swedish cohort study provide data that can be used to direct further research. The composite outcomes in HIE are lower than expected, and one could infer similar outcomes in high resource settings. The data are reassuring and will be useful for clinicians in counseling and reassuring parents with infants affected by mild HIE. Regarding a randomized controlled trial of therapeutic hypothermia in mild HIE: it would appear, based on the data provided by Törn et al., if we hypothesize this therapy would result in a 50% reduction in the composite outcome, the NNT would be approximately 50. This compares unfavorably to the NNT of 7 in moderate/severe HIE. Perhaps, further insight could be gained by review of individual patient data, particularly with respect to antenatal and neonatal course, imaging, EEG, and biochemical data in order to identify a subset that might benefit from therapeutic hypothermia or other novel therapy.Word count: 490
Objectives: To investigate the association and the potential value of prelabour fetal heart rate short-term variability (STV) determined by computerised cardiotocography (cCTG) and maternal-foetal Dopplers in predicting labour outcomes. Design: Prospective cohort study. Setting: The Prince of Wales Hospital, a tertiary maternity unit, in Hong Kong SAR. Population: Women with a term singleton pregnancy in latent phase of labour or prior to labour induction were recruited during May 2019 – November 2021. Methods: Ultrasonographic assessment of foetal growth, Doppler velocimetry and the cCTG monitoring including Dawes-Redman CTG analysis. Main Outcome Measures: Umbilical Cord arterial pH, emergency delivery due to pathological CTG during labour and neonatal intensive care unit (NICU)/special care baby unit (SCBU) admission. Results: Of the 400 cases, 34 (8.5%) women underwent emergency delivery for pathological CTG during labour. A total of 6 (1.50%) and 148 (37.00%) newborns required NICU and SCBU admission, respectively. Middle cerebral artery pulsatility index (MCA-PI) and MCA-PI z-score were significant lower in pregnancies that required emergency delivery for pathological CTG during labour compared with those who did not [1.23 (1.07-1.40) vs 1.40 (1.22-1.64), p=0.002 and 0.55 (±1.07) vs 0.12 (±1.06), p=0.049,]. Umbilical cord arterial pH was associated with STV (r = 0.107, p = 0.035) and the independent predictors for umbilical cord arterial pH were smoking (p = 0.006) and STV (p = 0.025). Conclusions: In pregnant women admitted in latent phase of labour or for induction of labour at term, cCTG STV is associated with umbilical cord arterial pH but not predictive of emergency delivery due to pathological CTG during labour.
Recent trends regarding GDM medication use have not been well described in prior literature. We identified pregnant patients enrolled in Tennessee Medicaid with a GDM diagnosis who a delivered in 2007 to 2019. We studied initial GDM medication use by delivery year (overall and by medication type). Over twenty percent of patients filled at least one prescription for GDM medication in the study period, with a significantly increasing prescribing trend over time. Starting in 2016, metformin replaced glyburide as the most common medication prescribed, which corresponds temporally with the emergence of evidence on the safety and effectiveness of different oral hypoglycemic medications and related changes in ACOG practice recommendations. These findings highlight how practice patterns have potential to shift quickly in response to evolving data.
Objective: To understand the extent to which adolescent awareness of and attitudes about anaemia and anaemia prevention can be changed by nutrition messages received at school. Design: Mixed-methods pre–post intervention study Setting: Three Government schools in Bagalkot, Belagavi and Raichur districts of Karnataka, India Population or Sample: Students of grade six and seven and teachers involved in implementing the intervention. Methods: An education intervention was co-developed by school teachers and nutrition experts using locally adapted resource materials that consisted of lectures, role play and practical demonstrations. Seven half-hour educational sessions were delivered by school teachers over seven weeks to 455 students. Pre- and post-intervention tests measured changes in adolescents’ knowledge about anaemia. In-depth interviews with teachers and focus groups with students explored reactions to the intervention. Main outcome measures: Knowledge score related to anaemia Results: The percentage of children with correct scores increased by 7.3 - 49.0 percentage points for the tested questions after implementation of the intervention. The mean knowledge score increased by 3.67±0.17(p<0.01). During interviews, teachers and students highlighted high acceptance of the intervention and materials, an increase in awareness, a positive attitude towards changing behaviour around diet, an increase in the demand for iron folic acid supplements and improved sharing of messages learned with peers and families. Challenges expressed included need for further training, time limitations and hesitancy in teaching about menstruation and pregnancy. Conclusions: Educational interventions carried out for adolescents by teachers in schools are effective in improving awareness and attitude related to anaemia.
Objective: Globally, early and optimal feeding practices and strategies for small and vulnerable infants are limited. We aim to share the challenges faced and implementation lessons learned from a complex, mixed methods research study on infant feeding. Design: A formative, multisite, observational cohort study using convergent parallel, mixed-methods design. Setting: 12 tertiary/secondary, public/private hospitals in India, Malawi, and Tanzania Population or Sample: Moderately low birthweight infants (MLBW; 1.50-2.49kg) Methods: We assessed infant feeding and care practices through: 1) assessment of in-facility documentation of 603 MLBW patient charts; 2) intensive observation of 148 MLBW infants during facility admission; and 3) prospective one-year follow-up of 1114 MLBW infants. Focus group discussions and in-depth interviews gathered perspectives on infant feeding among clinicians, families, and key stakeholders. Results: Hospital-level guidelines and provision of care for MLBW infants varied across and within countries. 89% of charts had missing data on time to first feed; 56% lacked discharge weights. Among 148 infants observed in-facility, 18.5% were discharged prior to meeting stated weight goals. Despite challenges during COVID, 90% of the prospective cohort was followed until 12 months of age. Conclusions: Enrolment and follow-up of this vulnerable population required additional effort from researchers and the community. Using a mixed-methods exploratory study allowed for a comprehensive understanding of MLBW health and evidence-based planning of targeted large-scale interventions. Multi-site partnerships in global health research, which require active and equal engagement, are instrumental in avoiding duplication and building a stronger, generalizable evidence base.
Monochorionicity in the absence of TTTS is not associated with an increased risk of adverse neurodevelopment at 5 years of age.Richard N Brown, MBBS, FRCOG, FACOGDirector of Obstetrics and Maternal Fetal Medicine, McGill University, McGill University Health Centre, Montreal, CanadaCorrespondence AddressRichard Brown, Division of Maternal Fetal Medicine, McGill University Health Centre, 1001 Decarie Blvd, Montreal, Canada H4A 3J1Richard.firstname.lastname@example.orgDisclosures: noneDespite stabilising twin pregnancy rates over the last two decades, as much as one birth in 30 is a twin birth. With twin preterm birth rates being as high as 60% (Martin et al, National Vital Statistics Reports;2019:68), prematurity represents the major factor influencing overall perinatal outcomes in twins. Monochorionicity (MC), with its attendant unique complications (including twin-to-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR)), represents another major risk factor for adverse perinatal outcome in twinning. MC complications contribute to the increased perinatal death rate evident in MC twins compared to dichorionic (DC) twins, as well as the greater premature birth rates [often iatrogenic] amongst MC twins. The potential for neurological harm associated with TTTS is now well understood, whilst in comparison that associated with growth discordance / sFGR or monochorionicity itself, remains less well established.Existing data have suggested increased rates of long-term neurodevelopmental deficits in MC twins overall and especially in those with growth discordance. Perinatal care of twins has improved significantly since data from cases followed in the 90’s reported an 8-fold greater risk of cerebral palsy (CP) in MC twins over DC twins, with this being 19-fold higher in MC twins with discordant growth (Adegbite et al AJOG 2004,190:156-63). A 37% rate of neurological damage has been reported even in the normally grown twin of an sFGR pair, when the co-twin has abnormal Dopplers; however, this was based on neuro-imaging findings within the first month and a half of life (Gratacos et al Ultrasound Obstet Gynecol 2004;24: 15-63). More recent data has shown a difference in mild neurological morbidities only, but follow-up, at a median of 24 months, ranged broadly from 12 months to 7 years (Rustico et al Ultrasound Obstet Gynecol 2017,49, 387-93). Despite the limitations of the available outcome data, such information underpins counselling in MC gestations complicated by sFGR. The question “will my twins be OK in the end?” remains one that is not easy to answer with confidence.The EPIPAGE2 cohort has the advantage of representing a more recent large national cohort of preterm births, recruited over a single year and with long term follow-up data. The sub-analysis presented here (Horau et al BJOG 2023, TBC), addresses the association of chorionicity and neurodevelopmental outcomes of prematurely delivered twins (22-34 weeks) at early school age (5 ½ years). The comprehensive testing likely paints a more realistic picture of the neurodevelopmental and neurobehavioural status of MC twins than these prior studies.Within the described population, 24% of twins were MC. The 20% of these complicated by TTTS were excluded from the outcome analysis given the known impact of TTTS. Growth discordance of 20% or more was found in 26.2% of the MC twins compared with 11.8% of the DC twins. In the context of a population with over a quarter of MC twins displaying significant growth discordance, the results are encouraging. Although fewer (68%) of MC twins were alive at discharge compared to DC twins (78%), the severe CP rates at 5 years were equivalent at around 1%. Amongst survivors there were no differences in the neuro-developmental or neuro-behavioural assessments between the MC and DC twins; with adverse outcomes seemingly therefore being linked principally to prematurity rather than chorionicity or growth discordance itself.
Evaluating Serum HE4: Some Serious ConsiderationsAimen Waqar Khana, Hussain Haider Shahba: Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.b: Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan.Dear Dr Papageorghiou,We have perused with great interest the scholarly article ”Serum HE4 predicts progestin treatment response in endometrial cancer and atypical hyperplasia: A prognostic study” by Chloe Barr et al. . We applaud the authors’ diligent efforts in investigating a biomarker that could independently predict the response to conservative therapy. However, we wish to draw attention to certain noteworthy aspects upon a comprehensive evaluation.Firstly, it is noteworthy that all the women who participated in the study underwent a preliminary endometrial biopsy before the initiation of progestin. However, there is no mention of whether women with relative contraindications such as cervical stenosis, coagulopathy or obstructive cervical lesions were sampled if they were included in the study. It is essential to consider these factors as they can significantly affect the accuracy and reliability of the biopsy results. Furthermore, it is necessary to note that insufficient tissue sampling is a common complication of endometrial biopsy, with an average of 31% of tissues obtained requiring improvement . Considering that this is typically more prevalent in postmenopausal women, and 61% of the participants were 50 years or older, it is crucial to standardize the volume of tissue obtained to ensure fair and precise results. As outlined in the study, the primary form of progestin therapy was levonorgestrel-releasing intrauterine system (LNG-IUS). Still, for women whose devices had been misplaced more than once, an alternative treatment of oral medroxyprogesterone acetate 500mg was administered twice daily. This raises a concern regarding whether these women were closely monitored for compliance with the prescribed treatment regimen. This is particularly important as non-compliance, particularly with extended oral therapies, is a common issue that, if present, could skew the study’s findings. The prognostic potential of pretreatment serum HE4 in predicting therapeutic response has been extensively researched; however, studies have also reported elevated serum HE4 levels in various other cancers, including ovarian, pancreatic, breast, lung, and stomach . Therefore, it is crucial to exclude such patients thoroughly, as their inclusion could lead to inaccurate results by falsely accounting for the non-responder count.Moreover, serum HE4 levels are also known to be influenced by renal function and status, necessitating adjustment . It is, therefore, essential to consider and standardize these factors when analyzing the serum HE4 levels to obtain reliable and valid results. Lastly, it should be noted that a CLEIA technique was employed for analysis, which has been reported to significantly overestimate serum HE4 as compared to EIA . This may raise concerns regarding the validity of the reported findings, and hence, caution must be exercised when interpreting the results.The study focused on endometrial biopsy in women receiving progestin therapy, but potential complications such as insufficient tissue sampling and the inclusion of women with contraindications were not addressed. The study primarily used LNG-IUS but also administered oral medroxyprogesterone acetate, and compliance monitoring was not discussed. Serum HE4 levels were examined, but patients with other cancers or renal issues were not excluded, and the CLEIA technique used for analysis may have overestimated results. Therefore, caution is necessary when interpreting the findings of this study.
Pelvic dimensions and hypotheses on duration of active second stage of labourTilde Broach OstborgStavanger University HospitalTM EggeboTrondheium University HospitalWe would like to thank Jan Novák and Petr Sedlak for their interest and comments to our manuscript. We found that increasing BMI was associated with shorter estimated median duration of the active second stage of labour.1We could not find any obvious causal mechanism for our findings; but suggested some possible explanations. The shorter active second stage may be related to increased abdominal pressure with increasing BMI, or perhaps increased strength when pushing.2, 3 Increased infiltration of fat in the muscular pelvic floor may decrease its strength and resistance.4 The presence of fat in the birth canal of obese women may delay the urge to bear down, thereby postponing active pushing until the head is lower in the maternal pelvis.Novak et al. measured the bi-ilac and bi-cristal diameters of the greater pelvis and found a broader pelvis in individuals with a history of obesity from adolescence.5 We supposed that there would be an association between the size of the greater pelvis and the size of the birth canal. We agree to the limitations commented by Novák and Sedlak. However, our proposed causal mechanisms are merely hypotheses, and cannot be accepted nor rejected based on current knowledge.1. Ostborg TB, Sande RK, Kessler J, Tappert C, von Brandis P, Eggebo TM. Put your weight behind it-Effect of body mass index on the active second stage of labour: A retrospective cohort study. BJOG. 2022;129:2166-2174.2. Lambert DM, Marceau S, Forse RA. Intra-abdominal pressure in the morbidly obese. Obes Surg. 2005;15:1225-1232.3. Tomlinson DJ, Erskine RM, Morse CI, Winwood K, Onambele-Pearson G. The impact of obesity on skeletal muscle strength and structure through adolescence to old age. Biogerontology. 2016;17:467-483.4. Pomian A, Lisik W, Kosieradzki M, Barcz E. Obesity and Pelvic Floor Disorders: A Review of the Literature. Med Sci Monit. 2016;22:1880-1886.5. Novak JM, Bruzek J, Zamrazilova H, Vankova M, Hill M, Sedlak P. The relationship between adolescent obesity and pelvis dimensions in adulthood: a retrospective longitudinal study. PeerJ. 2020;8:e8951.
Objective: To investigate programming effects of maternal testosterone on offspring birth anthropometrics. Design: Population-based prospective cohort study. Setting: University Hospital. Population: 1,486 mother-child dyads from Odense Child Cohort. Methods: Maternal blood samples were collected at gestational week 27-30 and free testosterone (FT) levels were calculated using the Vermeulen equation from total testosterone (TT) analyzed by mass spectrometry and sex hormone binding globulin (SHBG). Associations between FT or TT levels and birth anthropometrics were analyzed with multiple linear regression models according to offspring sex with adjustment for maternal age, parity, smoking and educational level. Analyses were repeated with polycystic ovary syndrome (PCOS) as exposure for offspring birth anthropometrics. Main outcome measures: Offspring birth weight (BW), birth length, abdominal- and head circumferences. Results: Maternal mean (SD) age was 30.2 (4.5) years and pre-pregnancy body mass index (BMI) was 23.5 (5.3) kg/m2. In boys (n=787), higher FT was associated with lower BW (adjusted doubling constant=-65.53, p=0.010), shorter birth length (adjusted doubling constant=-0.43, p<0.001), and lower abdominal circumference (adjusted doubling constant=-0.39, p<0.001); Higher TT was associated with lower abdominal circumference (adjusted doubling constant=-0.25, p=0.028). In girls, no associations were found between maternal FT or TT and offspring anthropometrics. Conclusions: Higher maternal free testosterone exposure was linked to reduced birth weight, length and abdominal circumference in boys, whereas girls were not susceptible to maternal testosterone exposure.