Fetal Size Classified Using Gestational Days rather than Gestational Weeks Improves Correlation with Stillbirth Risk: A Statewide Population Study.

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

Associations of Longitudinal Fetal Growth Patterns With Cardiometabolic Factors at Birth

BackgroundBirth weight is associated with cardiometabolic factors at birth. However, it is unclear when these associations occur in fetal life. We aimed to investigate the associations between fetal growth in different gestational periods and cord blood cardiometabolic factors.MethodsWe included 1,458 newborns from the Born in Guangzhou Cohort Study, China. Z-scores of fetal size parameters [weight, abdominal circumference (AC), and femur length (FL)] at 22 weeks and growth at 22–27, 28–36, and ≥37 weeks were calculated from multilevel linear spline models. Multiple linear regression was used to examine the associations between fetal growth variables and z-scores of cord blood cardiometabolic factors.ResultsFetal weight at each period was positively associated with insulin levels, with stronger association at 28–36 weeks (β, 0.31; 95% CI, 0.23 to 0.39) and ≥37 weeks (β, 0.15; 95% CI, 0.10 to 0.20) compared with earlier gestational periods. Fetal weight at 28–36 (β, −0.32; 95% CI, −0.39 to −0.24) and ≥37 weeks (β, −0.26; 95% CI, −0.31 to −0.21) was negatively associated with triglyceride levels, whereas weight at 28–36 weeks was positively associated with HDL levels (β, 0.12; 95% CI, 0.04 to 0.20). Similar results were observed for AC. Fetal FL at 22 and 22–27 weeks was associated with increased levels of insulin, glucose, and HDL.ConclusionsFetal growth at different gestational periods was associated with cardiometabolic factors at birth, suggesting that an interplay between fetal growth and cardiometabolic factors might exist early in pregnancy.

No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination

The impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities, and 2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from vaccinated murine pregnancies exhibit high circulating levels of anti-Spike and anti-RBD antibodies to SARS-CoV-2 consistent with maternal antibody status, indicating transplacental transfer. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.

A weighty issue: The implications of an ultrasound prediction of a large baby in pregnancy

Introduction: The assessment of fetal growth in Aotearoa New Zealand is governed by a largely medical model of care which highly values the purported objectivity of sonographic assessment. Ultrasound scans are an increasingly normalised part of pregnancy care, and expectant parents may advocate strongly for access to them. It could be questioned whether the increasing number of scans is aligned with clinical need. This paper presents a literature review that explores the implications of an ultrasound diagnosis of a large baby during pregnancy. Method: Databases searched were CINAHL, PubMed, Proquest, and Google Scholar. Search terms used were “macrosomia”, “large for dates” and “large for gestational age”. This search was first undertaken in May 2019, and then repeated in November 2020. Findings: Sonographic assessment of fetal size can be inaccurate and the existence of a predicted fetal weight on scan increases the likelihood of birth interventions, regardless of the baby’s actual size. While there are potentially negative outcomes associated with a larger baby, it is unclear whether birth interventions will significantly reduce the occurrence of these outcomes. There is limited research that focuses on the parents’ experience of having a predicted large baby, offering contradictory insights, which suggests the influence of conflicting meanings applied to large babies and ignoring the experiences of women whose babies were predicted to be large but were born “normal” sized. Discussion: Midwives are encouraged to openly discuss with women the limitations in available evidence in this area. Midwives can consider the context of the woman and whānau (wider family), and how they may assess risk uniquely. Finally, midwives can honour the woman and whānau as the decision-makers in their own experience. There are further opportunities for research to provide a counter-narrative to medicalising discourses about large babies, grounded in a midwifery belief in normal birth. Conclusion: Midwives and women are drawn into a risk-centric paradigm that pathologises large babies for questionable benefit. To support informed decision-making within the midwifery partnership, midwives need to critically evaluate existing research and communicate its limitations and risk-centric orientation.

Effect of PM2.5 Exposure On Gestational Hypertension and Fetal Size in Preeclampsia-Like Rats

Studies have reported that gestational PM2.5 exposure is associated with preeclampsia (PE) and fetal growth restriction (FGR). However, whether maternal exposure to PM2.5 causes adverse pregnancy outcomes is still largely unknown. Pregnant Sprague-Dawley rats were exposed to either filtered (FA) or PM2.5 air during the whole pregnant period. A PE-like rat model was established by intraperitoneal injection of L-NAME (300 mg/kg) from GD12 to until GD20. Systolic blood pressure (SBP), weight gain, pup weight and placental weight were measured. The percentages of rat Treg/Th17 cells and Th17-related cytokines were examined by flow cytometry. Gene expression profiles were analyzed by microarray, and the expression of differentially expressed genes were validated by qRT-PCR. The results showed that maternal PM2.5 exposure had no effect on SBP but was associated with LBW and a higher labyrinth/basal zone ratio. The percentages of splenic Th17 cells from the PM2.5 group in PE-like rats were higher than those from the FA or PM2.5 groups in healthy controls. A significantly decreased Treg/Th17 cell ratio was found in the PM2.5 group in PE-like rats. The mRNA expression of Foxp3 was downregulated, while the mRNA expression of RORα and RORγτ was upregulated after PM2.5 exposure. Furthermore, we observed that both the mRNA and protein expression of TNF-a, CCL2, CCL3 and CCR1 increased in the PM2.5 groups. Our study suggested that systemic inflammation may contribute to the development of FGR associated with PM2.5 exposure throughout pregnancy.

Female squirrel monkeys as models for research on women’s pelvic floor disorders

Animal models enable research on biological phenomena with controlled interventions not possible or ethical in patients. Among species used as experimental models, squirrel monkeys ( Saimiri genus) are phylogenetically related to humans and are relatively easily managed in captivity. Quadrupedal locomotion of squirrel monkeys resembles most other quadrupedal primates in that they utilize a diagonal sequence/diagonal couplets gait when walking on small branches. However, to assume a bipedal locomotion, the human pelvis has undergone evolutionary changes. Therefore, the pelvic bone morphology is not that similar between the female squirrel monkey and woman, but pelvic floor support structures and impacts of fetal size and malpresentation are similar. Thus, this review explores the pelvic floor support structural characteristics of female squirrel monkeys, especially in relation to childbirth to demonstrate similarities to humans.

Placental mitochondrial function, nutrient transporters, metabolic signalling and steroid metabolism relate to fetal size and sex in mice

Fetal growth depends on placental function, which requires energy supplied by mitochondria. Here we investigated whether mitochondrial function in the placenta relates to growth of the lightest and heaviest fetuses of each sex within the litter of mice. Placentas from the lightest and heaviest fetuses were taken to evaluate placenta morphology (stereology), mitochondrial energetics (high-resolution respirometry), and mitochondrial regulators, nutrient transporters, hormone handling and signalling pathways (qPCR and western blotting). We found that mitochondrial complex I and II oxygen consumption rate was greater for placentas supporting the lightest female fetuses, although placental complex I abundance of the lightest females and complexes III and V of the lightest males were decreased compared to their heaviest counterparts. Expression of mitochondrial biogenesis (Nrf1) and fission (Drp1 and Fis1) genes was lower in the placenta from the lightest females, whilst biogenesis-related gene Tfam was greater in the placenta of the lightest male fetuses. Additionally, placental morphology and steroidogenic gene (Cyp17a1 and Cyp11a1) expression were aberrant for the lightest females, but glucose transporter (Glut1) expression lower in only the lightest males versus their heaviest counterparts. Differences in intra-litter placental phenotype were related to sex-dependent changes in the expression of hormone responsive (androgen receptor) and metabolic signalling pathways (AMPK, AKT, PPARγ). Thus, in normal mouse pregnancy, placental structure, function and mitochondrial phenotype are differentially responsive to growth of the female and the male fetus. This study may inform the design of sex-specific therapies for placental insufficiency and fetal growth abnormalities with life-long benefits for the offspring.

Adrenal Cushing’s in Pregnancy, Managed with Metyrapone to Optimize for Adrenalectomy at 27 Weeks Gestation

Background: Cushing’s syndrome in pregnancy is associated with increased fetal and maternal morbidity and mortality. Prompt diagnosis and management during pregnancy is critical to improving these outcomes. Clinical Case: Patient is a 28-year-old female who presented to our hospital at 25 weeks of pregnancy with severe striae, high blood pressure, mildly elevated blood sugars and hypokalemia. Striae began in the 6th week of her pregnancy but progressed in the 2nd trimester to encompass multiple sections of skin. Blood pressure on presentation was 146/100 mmHg (on labetalol) and fasting glucose 113 mg/dL (goal &lt;95 mg/dL in pregnancy). Labs were consistent with ACTH-independent Cushing’s Syndrome: AM serum cortisol of 42.3 mcg/dL (n &lt; 22.6 mcg/dL), PM serum cortisol of 46 mcg/dL (n &lt; 11.9 mcg/dL), ACTH of &lt;1 pg/mL (normal 7–63 pg/mL), 24-hour urinary free cortisol of 1388 mcg/day (n &lt;45 mcg/day), and salivary midnight cortisol of 2.2 mcg/dL (n &lt;0.3 mcg/dL). An abdominal MRI scan without contrast showed a 3.2 cm fat-containing right adrenal lesion consistent with an adenoma. The fetus was large for gestational age at 98th percentile. Patient was started on metyrapone 250 mg twice daily, which was titrated up to 250 mg three times daily. Her blood pressure and glucose levels, treated with labetalol and insulin respectively, improved on metyrapone. Surgery, Maternal Fetal Medicine, Endocrine, Anesthesia, and Neonatal physicians reviewed her case at an interdisciplinary meeting. She received metyrapone for 1 week pre-operatively. AM serum cortisol improved to 21.4 mcg/dL and 24-hour urinary free cortisol improved to 139 mcg/day. She underwent laparoscopic right adrenalectomy at 27 weeks of pregnancy. Betamethasone was given 2 days prior to ensure fetal lung maturity in case of preterm labor. Stress dose hydrocortisone 100 mg was given intra-operatively. Fetal heart monitoring was normal throughout the surgery and post-operatively. After surgery, metyrapone was stopped and hydrocortisone was tapered to 20 mg and 10 mg. Five weeks after her adrenalectomy, striae decreased in size and glucoses normalized. Remarkably, fetal size is now appropriate for gestational age in the 62th percentile at 34 weeks. However, blood pressure remains elevated and is being treated with labetalol. She is planned for induction of labor at 37 weeks due to her elevated blood pressures and will be given stress dose steroids intraoperatively. Conclusion: Medical management of adrenal Cushing’s in pregnancy with metyrapone followed by adrenalectomy required a multidisciplinary team approach. Patient underwent successful adrenalectomy without complications of severe hypercortisolism, including infection, thromboembolism, pre-eclampsia, preterm labor and pregnancy loss. After surgery, there was normalization of maternal blood sugars as well as fetal size, and persistent, but improved, elevated blood pressure.