Objective: To study the outcomes of new pregnancies after previous complete uterine rupture. Design: Descriptive study based on population data from the Medical Birth Registry of Norway, the Patient Administration System, and medical records. Sample: Maternities with previous complete uterine rupture in Norway during the period 1967–2011 (N=72), extracted from 2 455 797 maternities. Method: We measured the rate of new complete ruptures and partial ruptures, as well as the maternal and perinatal outcomes of these pregnancies. The characteristics of both previous ruptures and new ruptures were described. Results: Among 72 maternities, there were thirty-seven with previous ruptures in the lower segment (LS) and 35 outside the LS. We found three new complete ruptures and six uneventful partial ruptures, resulting in a rate of 4.2% and 8.3%, respectively. All three complete ruptures occurred preterm in scars outside the LS. The rate of new complete rupture was 0% in those with previous rupture in the LS, and 8.6% in previous ruptures outside the LS. The corrected perinatal mortality was 1.3%, and prematurity (<37 weeks) was high (36.1%); this was noticed even in the absence of new ruptures and was mostly iatrogenic. Two hysterectomies were performed in the absence of rupture and two cases had abnormal invasive placenta. Conclusion: The prognosis for pregnancies after previous complete uterine rupture is favorable. Prematurity is a problem caused by both obstetrician and mother anxiety, so the timing of delivery is most challenging. Careful counseling, vigilance for symptoms, and immediate delivery are most important.

Objective Describe changes over time regarding mode of birth and perinatal outcomes in women with one previous caesarean section in the Netherlands over the past 20 years. Design Population-based study. Setting Nationwide. Population All women with one previous caesarean section and no previous vaginal birth, who gave birth to a term singleton in cephalic presentation between 2000 and 2019 (n=143,308). Methods Analysis of Dutch perinatal registry data. Main outcome measures Primary: mode of birth per year, intended vaginal birth versus planned caesarean section. Secondary: failed versus successful vaginal birth in case of intended vaginal birth after caesarean (VBAC), and adverse perinatal outcome (perinatal mortality up to 28 days, low Apgar score at 5 minutes, asphyxia, and NICU admission >24 hours). Results A decrease of 21.5% was seen in women with one previous caesarean section intending VBAC in a subsequent pregnancy, from 77.2% in 2000 to 55.7% in 2019, with a marked acceleration from 2009 onwards. The VBAC success rate dropped gradually, from 71.0% to 65.3%. Overall caesarean section rate (planned and unplanned) increased from 45.1% to 63.6%. Adverse perinatal outcomes were higher in women intending VBAC compared to planned caesarean section. However, after an initial decrease, perinatal mortality remained stable from 2009 onwards with only a minimal difference between both modes of birth. Conclusions In the Netherlands, the proportion of women intending VBAC after a previous caesarean section has decreased markedly, particularly from 2009 onwards. This decrease was not accompanied by a synchronous decrease in perinatal mortality after that year.

Objective: To determine the prevalence of pre-eclampsia and fetal growth restriction (FGR; <3rd centile) in women with pre-existing cardiac dysfunction. Design: Retrospective cohort study. Setting: Maternity units in UK and Australia. Population: Pregnant women with impaired left ventricular ejection fraction<55%. Methods: Routine clinical data, including medical history and pregnancy outcome were collected retrospectively. Main Outcome Measures: Pre-specified outcomes included pre-eclampsia and FGR prevalence in women with pre-existing cardiac impairment, compared with the general population; and the relationship between pregnancy outcome and pre-pregnancy cardiac phenotype. Results: In this cohort of 282 pregnancies, pre-eclampsia prevalence was not significantly increased (4.6% [95% C.I 2.2-7.0%] versus population prevalence of 4.6% [95% C.I. 2.7-8.2], p=0.99); 12/13 of these women had additional obstetric/medical risk factors. However, prevalences of preterm pre-eclampsia (<37 weeks) and FGR were increased (1.8% versus 0.7%, p=0.03; 15.2% versus 5.5%, p<0.001, respectively). Neither systolic nor diastolic function correlated with pregnancy outcome; however, left ventricular mass index (LVMi) weakly correlated with pre-eclampsia (5g/m2 increase: OR 1.18 [95% C.I. 1.01-1.38], p=0.04). Antenatal ß blockers (n=116) were associated with lower birthweight Z score (adjusted difference -0.33 [95% C.I. -0.63- -0.02], p=0.04). Conclusions: This study demonstrated a modest increase in preterm pre-eclampsia and significant increase in FGR in women with cardiac dysfunction. These results do not support a causal relationship between cardiac dysfunction and pre-eclampsia, especially accounting for the background risk status of the population. The mechanism underpinning the relationship between cardiac dysfunction and FGR merits further research but could be influenced by concomitant ß blocker use.

OBJECTIVE: Our goal is to describe the association between total quantitative blood loss (QBL) and risk of obstetric hemorrhage-related morbidity (OBH-M) in order to assess utility of the current definition of obstetric hemorrhage (OBH). DESIGN: Retrospective cohort study. SETTING: Urban safety-net hospital in Boston, Massachusetts. POPULATION or SAMPLE: Deliveries at our institution over a two-year period. METHODS: We categorized deliveries into ten equally sized deciles based on QBL and compared the proportion with OBH-M in each. Among the two deciles with the highest proportions of OBH-M, we stratified deliveries into seven groups of ascending intervals of 250cc QBL. Finally, we compared the positive predictive value (PPV) of the standard definition of OBH (QBL ≥ 1000cc) to a definition extrapolated from our stratified analysis. MAIN OUTCOME MEASURES: The primary outcome was proportion of deliveries within each QBL decile affected by OBH-M. The secondary outcome was PPV. RESULTS: We found a significant increase in OBH-M from decile 9 (895-1201cc QBL) to decile 10 (1205-8325cc QBL) (p<0.001). In our stratified analysis, we found QBL of 1500cc to be an inflection point for an increased proportion of OBH-M. Our secondary analysis showed an increased PPV for OBH-M using QBL of 1500cc (20.5%) compared to that of QBL 1000cc (9.8%). CONCLUSIONS: Our findings suggest that a higher QBL threshold than the currently accepted definition of OBH is more predictive of OBH-M.

Objective: international validation of the Dutch Delphi consensus study about which anatomical structures that should be taught to ensure safe and competent practice among general gynaecologists. Design: Validation study. Setting: Academic, non-academic teaching and non-academic, non-teaching hospitals worldwide. Population: Gynaecologists and trainees in gynaecology. Methods: The relevance of 123 items included in the Dutch Delphi study was scored on a Likert scale between 1 (not relevant) and 5 (highly relevant). Consensus was defined when  70% of the panellist scored the item as relevant or very relevant and the average rating was  4. Main Outcome Measures: Clinically relevant anatomical structures. Results: A total of 192 gynaecologists and trainees from seven countries (Belgium, Germany, Norway, Oceania, Sweden, United Kingdom and United States) completed the questionnaire. Of the 123 structures, 72 (58.5%) were internationally relevant. When the 72 relevant structures from the international Delphi study were compared with the 86 relevant structures from the Dutch Delphi study, 70 (81.4%) structures matched. Conclusions: This study identified 70 anatomical structures that should be taught for safe and competent practice of general gynaecologists based on national and international validation. The results of our study identify the learning needs (i.e., the content) for an international anatomy curriculum. The development of the curriculum (i.e., the form) can be determined by each country and used to standardize and guide postgraduate training in gynaecology. This is an important step in the era of international teaching and training.

Objective: To study the association between mode of conception and risk of preterm birth (PTB), including, spontaneous and provide-initiated PTB. Design: Retrospective cohort study Setting and Population: Population-based cohort included all singleton livebirths and stillbirth in Ontario, Canada, 2006-2014. Methods: Mode of conception comprised (i) subfertility without infertility treatment (N = 68,822); (ii) non-invasive infertility treatment (ovulation induction +/- intrauterine insemination) (N = 9024); or (iii) Invasive infertility treatment (in vitro fertilization [N = 8038) – each compared to births by unassisted conception (N = 646,926). Modified Poisson regression generated risk ratios (RR). Confounding was handled by inverse probability of treatment weighting using a propensity that included maternal demographics and pre-existing conditions. Main Outcome Measure: PTB < 37 completed weeks’ gestation. PTB was further categorized as spontaneous PTB or provider-initiated PTB. Results: PTB occurred among 6.0% of births by unassisted conception, 7.7% with subfertility, 8.0% with non-invasive infertility treatment, and 10.8% following invasive infertility treatment. The RR of provider-initiated PTB was higher in women with subfertility (RR 1.23, 95% CI 1.16-1.31), non-invasive infertility treatment (RR 1.48, 1.29-1.69) and invasive infertility treatment (RR 2.35, 2.09-2.64) – each relative to births by unassisted conception. The corresponding RR for spontaneous PTB were 1.15 (95% CI 1.10-1.19), 1.19 (95% CI 1.09-1.31) and 1.40 (95% CI 1.27-1.53). Conclusions: Subfertility, and receipt of infertility treatment, are each associated with a higher risk of PTB, especially provider-initiated PTB. Strategies are needed to reduce the underlying indications to deliver these women before term.

ABSTRACT Background: Obstetrical complications involving uteroplacental insufficiency associated disorders, such as preeclampsia, intrauterine growth restriction, and obstetric antiphospholipid syndrome, share pathophysiology and risk factors with cardiovascular diseases treated with statins. Objective: To evaluate associations of statin treatment with pregnancy prolongation, and neonatal and maternal morbidity, among women with uteroplacental insufficiency disorders. Search Strategy: Electronic databases including PubMed, Medline, Embase, Clinical Trials Registry Clinicaltrials.gov, and The Cochrane Library were searched from inception to January 2022. Selection Criteria: Cohort studies and randomized controlled trials (RCTs) Data collection and analysis: Pooled odds ratios were calculated using a random-effects model; meta-regression was utilized when applicable. Main Results: The analysis included ten studies describing 1391 women with uteroplacental insufficiency-associated disorders: 703 treated with pravastatin and 688 not treated with statins. Women who received pravastatin showed significant prolongation of pregnancy (mean difference 0.44 weeks, 95%CI:0.01-0.87, p=0.04, I2=96%) and less neonatal critical care unit admission (OR=0.42, 95%CI: 0.23-0.75, p=0.004, I2=25%). Trends were observed toward a decrease in preeclampsia diagnoses (OR=0.51, 95%CI:0.25–105, p=0.07, I=44%), and perinatal death (OR=0.32, 95%CI:0.09-1.13, p=0.08, I2=54%) and an increase in birth weight (mean difference=102 grams, 95%CI: -14–212, p=0.08, I2=96%). A meta-regression analysis revealed associations between earlier gestational age at initiation of pravastatin treatment to lower risk for development of preeclampsia (R2=1) and between longer duration of pravastatin treatment to lower rate of NICU admission (R2=0.33). No dose-response effect was demonstrated. Conclusions: Pravastatin treatment in pregnancies with high risk for developing uteroplacental insufficiency disorders may prolong pregnancy duration and improve neonatal outcomes.

Objective: Many growth charts provide single centile cutoffs for each week of gestation, yet fetuses gain weight throughout the week. We aimed to assess whether using a single centile per week distorts the proportion of infants classified as small and their risk of stillbirth across the week. Design: Retrospective cohort study. Setting: Victoria, Australia. Population: Singleton, non-anomalous infants born from 2005-2015 (529,261). Methods: We applied growth charts to identify small-for-gestational-age (SGA) fetuses on week-based charts (single centile per gestational week) and day-based charts (centile per gestational day). Main outcome measures: Proportions <10th centile by each chart, and stillbirth risk amongst SGA infants. Results: Using week-based charts, 12.1% of infants born on the first day of a gestational week were SGA, but only 7.8% on the final day; ie. an infant born at the end of the week was 44% less likely to be classed as SGA (p<0.0001). The relative risk of stillbirth amongst SGA infants born on the final day of the week compared with the first was 1.47 (95%CI 1.09-2.00, p=0.01). Using day charts, SGA proportions were similar and stillbirth risk equal between the beginning and end of the week (9.5% vs 9.9%). Conclusions: Growth standards using a single cutoff for a gestational week overestimate the proportion of infants that are small at the beginning of the week and underestimate the proportion at the end. This distorts the risk of stillbirth amongst SGA infants based on when in the week an infant is born. Day-based charts should be used

Objective: To develop and validate a predictive model assessing the risk of cesarean delivery in primiparous women based on the findings of magnetic resonance imaging (MRI) studies. Design: Observational study Setting: University teaching hospital. Population: 168 primiparous women with clinical findings suggestive of cephalopelvic disproportion. Methods: All women underwent MRI measurements prior to the onset of labor. A nomogram model to predict the risk of cesarean delivery was proposed based on the MRI data. The discrimination of the model was calculated by the area under the receiver operating characteristic curve (AUC) and calibration was assessed by calibration plots. The decision curve analysis was applied to evaluate the net clinical benefit. Main Outcome Measures: Cesarean delivery. Results: A total of 88 (58.7%) women achieved vaginal delivery, and 62 (41.3%) required cesarean section caused by obstructed labor. In multivariable modeling, the maternal body mass index before delivery, induction of labor, bilateral femoral head distance, obstetric conjugate, fetal head circumference and fetal abdominal circumference were significantly associated with the likelihood of cesarean delivery. The discrimination calculated as the AUC was 0.845 (95% CI: 0.783-0.908; P < 0.001). The sensitivity and specificity of the nomogram model were 0.918 and 0.629, respectively. The model demonstrated satisfactory calibration. Moreover, the decision curve analysis proved the superior net benefit of the model compared with each factor included. Conclusion: Our study provides a nomogram model that can accurately identify primiparous women at risk of cesarean delivery caused by cephalopelvic disproportion based on the MRI measurements.

Objective: The objective of this study is to establish maternal reference values of AMH in a fertile multi-ethnic urban pregnant population and to evaluate the effect of gestational age. Design: The Generation R Study is an ongoing population-based prospective cohort study from early pregnancy onwards. Setting: Rotterdam, the Netherlands, out of hospital setting. Population: In 5806 women serum AMH levels were determined in early pregnancy (median 13.5 weeks; 95% range 10.5-17.2). Methods: The model-based AMH reference ranges for maternal age and gestational age were created using GAMLSS. Associations between AMH and several first trimester biomarkers were analyzed using multivariate linear regression analyses. Main outcome measures: AMH levels in early pregnancy and the association with placental biomarkers, hCG, sFLT, and PLGF. Results: A nomogram of AMH in early pregnancy was developed. Serum AMH levels showed a decline with advancing gestational age. Higher AMH levels were associated with a higher level of hCG and sFLT. This last association was predominantly mediated by hCG. AMH levels were negatively associated with PLGF levels. Conclusion: In this large study we show that AMH levels in the first trimester decrease with advancing gestational age. The association between AMH and the placental biomarkers hCG, sFLT and PLGF suggests a better placental development with a lower vascular resistance in mothers with higher AMH levels. AMH might be useful in predicting adverse pregnancy outcome due to impaired placental development. Keywords: Ovarian reserve, placental biomarker, nomogram, first trimester, human Choriogonadotrophin (hCG), soluble FMS-Like Tyrosine kinase-1 (sFLT), Placental Growth Factor (PLGF).

OBJECTIVE(S): to evaluate the severity of HDFN in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. DESIGN: prospective cohort. SETTING: the Netherlands. POPULATION: nationwide selection of all pregnant women with RhD antibodies. METHODS: women with two subsequent RhD immunized pregnancies with RhD-positive children after antibodies were detected were included. MAIN OUTCOME MEASURE: the severity of HDFN in the first and subsequent pregnancy at risk. RESULTS: 62 RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased significantly in the subsequent pregnancy (P<.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, severe HDFN in the next pregnancy was uncommon (22%), especially when no therapy or only non-intensive phototherapy was indicated during the first pregnancy (6%), or if the ADCC result remained <10%. Contrarily, women with antibodies detected during the first pregnancy of a RhD positive child (>= 27th week), most often before they had ever received RhIg prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). CONCLUSION(S): RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of a RhD-positive child are at highest risk of severe disease in the next pregnancy.

Background: Concerns about virus spread during surgery contributed to changes in the clinical management of ectopic pregnancies (EP) during the COVID19 pandemic. Objective: To compare published data on EP management prior versus during the COVID-19 pandemic and evaluate any difference in the management, rupture rate and complications where Early Pregnancy Unit (EPU) structures exist. Search strategy: We performed a systematic review of the literature using a keyword strategy based on our PICO criteria. Selection criteria: We included studies which recruited women diagnosed with ectopic pregnancy and compared the management during and prior the COVID-19 pandemic peak. Data collection and Analysis: Three independent reviewers screened the literature and extracted the data. Meta-analysis of the data was performed on Revman. Main Results: Our search yielded 34 studies; 12 were included in our meta-analysis (3122 women). We found no difference in the type of management of EP between the pre-Covid and Covid cohorts [2714 women, OR 0.99(0.63-1.55), p=0.96, I2=77%]. We observed a non-statistically significant reduction of surgical management within the EPU branch ([OR 0.47(0.19-1.13), p=0.09, I2=81%]). There was no difference in the ectopic rupture rate in units with EPU [OR= 0.66 (0.33-1.31), p=0.24, I2=37%]. In contrast, in non-EPU (NPEU) the risk of ruptured EP [OR=2.86(1.84-4.46), p<0.01 I2=13%] and complications [OR=1.69(1.23-2.31), p=0.001, I2=45%] were increased. Conclusions: The worldwide trend was not reflected in the UK suggesting that EPU may have contributed to prompt diagnosis and safe management of EP. Funding: No funding was received. Keywords: ectopic pregnancy, COVID 19, meta-analysis, early pregnancy unit

Background The interconception period is considered a time when parents are likely to engage with health messages and are in frequent contact with healthcare professionals. Objectives Through this literature review and policy analysis, we synthesised articles and guidelines on interconception care to provide recommendations to improve health outcomes for parents, infants and future generations. Search Strategy Four databases were searched systematically, using MeSH and free-text terms based on ‘interconception’ and ‘postpartum’. Selection Criteria Selected articles included reviews, pilot studies and guidelines on interconception and postpartum interventions published in English by UK public health organisations and government agencies between 1st January 2010-12th January 2021. Data Collection and Analysis 30% of titles, abstracts and full-text papers were double-screened. The description table of identified guidelines were qualitatively analysed to generate categories, later developed into a framework of six domains. Findings are described using a narrative synthesis approach. Main Results We found 47 documents with guidelines, 29 reviews and six pilot studies on interconception and postpartum care. Interconception care opportunities include the postpartum period, family planning, routine practice, and risk assessments. Health and non-healthcare professionals have a role to play in the interconception period including GPs, health visitors, dieticians, nutritionists, health psychologists, community groups, local authorities and charities such as Tommy’s and First Step Nutrition. Conclusions The interconception and postpartum periods offer crucial opportunities to intervene to reduce possible long-term effects of suboptimal nutrition. Though the policy analysis for this review focused on the UK, the recommendations can have wider implications for other countries.

Objective: To compare emergency department (ED) presentations and hospital admissions for urgent early pregnancy conditions in Victoria before and after the onset of COVID-19 lockdown on 31 March 2020. Design: Population-based retrospective cohort study Setting: Australian state of Victoria Population: Pregnant women presenting to emergency departments or admitted to hospital Methods: We obtained state-wide hospital separation data from the Victorian Emergency Minimum Dataset and the Victorian Admitted Episodes Dataset from January 1, 2018, to October 31, 2020. A linear prediction model based on the pre-COVID period was used to identify the impact of COVID restrictions. Main outcome measures: Monthly ED presentations for miscarriage and ectopic pregnancy, hospital admissions for termination of pregnancy, with subgroup analysis by region, socioeconomic status, disease acuity, hospital type. Results: There was an overall decline in monthly ED presentations and hospital admissions for early pregnancy conditions in metropolitan areas where lockdown restrictions were most stringent. Monthly ED presentations for miscarriage during the COVID period were consistently below predicted, with the nadir in April 2020 (790 observed vs 985 predicted, 95% CI 835-1135). Monthly admissions for termination of pregnancy were also below predicted throughout lockdown, with the nadir in August 2020 (893 observed vs 1116 predicted, 95% CI 905-1326). There was no increase in ED presentations for complications following abortion, ectopic or molar pregnancy during the COVID period. Conclusions: Fewer women in metropolitan Victoria utilized hospital-based care for early pregnancy conditions during the first seven months of the pandemic, without any observable increase in maternal morbidity.

Objective. Clinicians and regulators are receiving reports of changes to menstrual periods following COVID-19 vaccination. However, it is unclear if the two are biologically linked. If they are, people using hormonal contraception are predicted to be less likely to report a change and spontaneously cycling people vaccinated prior to ovulation more likely. The objective was to test these hypotheses. Design. Retrospective cohort study. Setting. UK. Population. 1273 people who had received at least one dose of a COVID-19 vaccination, have periods or withdrawal bleeds and keep a record of the dates of these. Methods. Participants reported whether they use any hormonal contraception and, for each dose of the vaccine, on which day of their menstrual cycle they were vaccinated and details of how the timing and flow of their next period compared to their normal experience. Main outcome measures. Association between 1. the use of hormonal contraception and reported changes to timing or flow of the next menstrual period, and 2. the timing of vaccination within the menstrual cycle and reported changes to timing or flow of the next menstrual period. Results. The data from this cohort did not support the pre-specified hypotheses that people using hormonal contraception would be less likely to report a change, or that spontaneously cycling people vaccinated prior to ovulation would be more likely to report a change. Conclusions. This study did not detect strong signals supporting the idea that COVID-19 vaccination is linked to menstrual changes in most people. Funding. No specific funding.

Objective No study ever investigated the long-term risk of stroke in women with pre-eclampsia/eclampsia. The purpose of this study is to explore long-term stroke risks, differentiating subtypes and their time trends. Design Nationwide population-based cohort study Methods Between 2000 and 2017, 1,384,427 pregnant women were registered in the National Health Insurance Research Database in Taiwan. After excluding women with previous stroke history and exact matching with all confounders, 6,053 women with pre-eclampsia/eclampsia and 24,212 controls were recruited. Main Outcome Measures Hemorrhagic and ischemic strokes after child-birth Results Over the 17-year follow-up, the adjusted hazard ratio (aHR) for stroke in women with a history of pre-eclampsia/eclampsia was 2.05 (95% confidence interval, CI = 1.67-2.52, p<0.001). The 17 years overall risks of both ischemic and hemorrhagic stroke were 1.98 and 3.45, respectively (p<0.001). The stroke subtypes, hemorrhagic and ischemic, had different time trend risks, and hemorrhagic stroke risks kept higher than that of ischemic stroke. The ischemic stroke risk peaked during 1-3 years after childbirth (aHR=3.09). The hemorrhagic stroke risk peaked during 3-5 years (aHR=7.49). Conclusions Stroke risk persisted even after decades, for both ischemic and hemorrhagic subtypes. Women with pre-eclampsia/eclampsia history should be aware of the long-term risk of stroke. Tweetable abstract Both ischemic and hemorrhagic stroke risks persisted high even after decades, while their time trend risks were different. Keywords: pre-eclampsia/eclampsia; ischemic stroke; hemorrhagic stroke

Objective: Identify the proportion of infants reclassified if sex-specific birthweight charts were used, and if this reclassification has an impact on the correlation between birthweight centile and adverse perinatal outcome. Design: Retrospective cohort study Setting: Victoria, Australia. Population: All infants born from 2005-2015 (529,261) Methods: We applied GROW centiles, either adjusted or unadjusted for fetal sex. We compared proportions of small for gestational age (SGA, <10th centile) infants, then the populations of males considered small only by sex-specific charts and females considered small only by unadjusted charts. Main Outcome Measures: Stillbirth, combined perinatal mortality, NICU admissions, Apgars <7 at 5 minutes, emergency caesarean sections. Results: Of those <10th centile by unadjusted charts, 39.6% were male, and 60.5% female. Using sex-specific charts, 50.3% <10th centile were male and 49.7% female. 9,449 (19.2%) females that were SGA according to unadjusted charts were appropriate for gestational age (AGA,>10th-<90th centile) using sex-specific charts. These reclassified newborn females were not at increased risk of adverse outcomes compared with an AGA infant, but were at increased risk of being iatrogenically delivered for suspected growth restriction (RR 4.90, 95%CI 4.39–5.48). 8,048 male infants were reclassified as SGA by sex-specific charts (25% SGA increase). Compared with AGA infants, these reclassified male newborns were at greater risk of stillbirth (RR 1.94, 95%CI 1.30-2.90) and all other adverse perinatal outcomes. Conclusions: Sex-specific growth standards classify a new high-risk cohort of male infants as SGA, and exclude a cohort of females, whose risk is no greater than appropriately grown infants.

Objective: Evaluate the impact of the timing of SARS-CoV-2 infection on pregnancy outcomes in a low-middle income setting. Design: two parallel, observational studies. Setting and population: pregnant women or women presenting for labour, enrolled between April-September 2020, in South Africa. Methods: i) longitudinal follow-up study of symptomatic or asymptomatic pregnant women investigated for SARS-CoV-2 infection antenatally, ii) cross-sectional study of SARS-CoV-2 infection at time of labour. SARS-CoV-2 infection was investigated by nucleic acid amplification test (NAAT). Main Outcome Measures: association of SARS-CoV-2 infection on nasal swab and birth outcomes. Results: Antenatally, 793 women were tested for SARS-CoV-2. Overall SARS-CoV-2 infection was confirmed in 138 women, including 119/275 with symptomatic illness (COVID-19) and 19/518 asymptomatic women; 493 women were asymptomatic and SARS-CoV-2 non-reactive. Women with COVID-19 were 1.66-times (95%CI: 1.02, 1.71) more likely to have a low-birthweight newborn (30%) compared to asymptomatic women without SARS-CoV-2 (21%). Overall, 3117 women were tested for SARS-CoV-2 infection at delivery, including 1560 healthy women with an uncomplicated term delivery. Adverse birth outcomes or pregnancy-related complications were not associated with infection at delivery. Among women with SARS-CoV-2 infection at delivery, NAAT was reactive on 6/98 of maternal blood samples, 8/93 of cord-blood, 14/54 of placentas and 3/22 of nasopharyngeal swabs from newborns collected within 72-hours of birth. Conclusions: Antenatal, but not intrapartum, SARS-CoV-2 infection was associated with low-birthweight delivery. Maternal infection at the time of labour was associated with in utero foetal and placental infection, and possible vertical and/or horizontal viral transfer to the newborn.