Neonatal outcomes after in utero exposure to antipsychotics: a systematic review and meta-analysis.

Adverse neonatal outcomes following in utero antipsychotic exposure remain unclear. This systematic review and meta-analysis aimed to investigate associations between in utero first- and second-generation antipsychotic exposure and various neonatal outcomes. The primary outcome was small for gestational age. Secondary outcomes included other birth weight-related measures, prematurity and neonatal outcomes. MEDLINE, EMBASE, CENTRAL, ICTRP, and ClinicalTrials.gov were searched for on 8th July 2023. Two reviewers independently selected studies reporting associations between exposure and neonatal outcomes (all designs were eligible, no language or time restriction) and extracted data. ROBINS-I was used for risk of bias assessment. Meta-analyses were performed. Measures of association were odds ratios and mean differences. Thirty-one observational studies were included. Regarding small for gestational age < 10th percentile, meta-analysis was only performed for second-generation antipsychotics and showed no evidence for an association (OR 1.31 [95%CI 0.83; 2.07]; I²=46%; phet=0.13, n = 4 studies). First-generation antipsychotics were associated with an increased risk of small for gestational age < 3rd percentile (OR 1.37 [95%CI 1.02; 1.83]; I²=60%; phet=0.04, n = 5) and a lower mean birthweight (MD -135 g [95%CI -203; -66]; I²=53%; phet=0.07, n = 5). Second-generation antipsychotics were associated with large for gestational age > 97th percentile (OR 1.56 [95%CI 1.31; 1.87]; I²=4%; phet=0.37, n = 4) and Apgar score < 7 (OR 1.64 [95%CI 1.09; 2.47]; I²=47%; phet=0.13, n = 4). Both types of antipsychotics were associated with increased risks of preterm birth and neonatal hospitalization. Despite potential confounding in the studies, this systematic review and meta-analysis showed that newborns of mothers using antipsychotics during pregnancy are potentially at risk of adverse neonatal outcomes. Data sources: MEDLINE, EMBASE, CENTRAL, ICTRP, ClinicalTrials.gov. Prospero Registration Number CRD42023401805.

Obstetric and neonatal outcomes in women with Ankylosing spondylitis - an evaluation of a population database.

BACKGROUND: Ankylosing Spondylitis (AS) is a systemic chronic rheumatic disease characterized by involvement of the axial skeletal and sacroiliac joints. Although this disease is not rare amongst women of reproductive age, data regarding pregnancy outcomes have demonstrated conflicting results. We therefore aimed to compare pregnancy and perinatal outcomes between women who suffered from AS to those who did not. METHODS: A retrospective cohort study using the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS). Included in the study were all pregnant women who delivered or had a maternal death in the US between 2004 and 2014. Women with an ICD-9 diagnosis of AS before or during pregnancy were compared to those without. Pregnancy, delivery, and neonatal outcomes were compared between the two groups using multivariate logistic regression models adjusting for potential confounders. RESULTS: A total of 9,096,788 women were inclusion in the analysis. Amongst them, 383 women (3.8/100,000) had a diagnosis of AS and the rest were controls. Women with AS, compared to those without, were more likely to be older; Caucasian; from higher income quartiles; suffer from thyroid disorders, and have multiple pregnancies (p < 0.001, all). After adjusting for confounders, patients in the AS group, compared to those without, had a higher rate of cesarean delivery (CD) (aOR 1.47, 95% CI 1.14-1.91, p = 0.003); gestational diabetes (aOR 1.55, 95% CI 1.02-2.33, p = 0.038); and placenta previa (aOR 3.6, 95% CI 1.6-8.12, p = 0.002). Regarding neonatal outcomes, patients with AS, compared to those without, had a higher rate of small-for-gestational-age (SGA) neonates (aOR 2.19, 95% CI 1.22-3.93, p = 0.009); and intrauterine fetal death (IUFD) (aOR 3.46, 95% CI 1.11-10.83, p = 0.033). CONCLUSION: Women diagnosed with AS have an increased risk of obstetric complications, including CD, as well as an increased risk of SGA and IUFD.

Neonatal sex and maternal factors associated with small-for-gestational-age neonates: A nationwide population-based study.

Background and Aims: Small-for-gestational-age (SGA) newborns have a higher risk of morbidity and mortality. Recognizing the risk factors for SGA helps raise early awareness of the issue and provides valuable insights for both healthcare providers and pregnant women. We aimed to identify determinants of SGA using population-based databases in Taiwan. Methods: Data were retrieved from the National Health Insurance, Birth Reporting, and Maternal and Child Health databases for this nationwide case-control study. Live births between 20 and 44 weeks of gestation from 2005 to 2014 were enrolled and linked to their mothers to determine maternal conditions during pregnancy. For every SGA newborn, four controls matched by gestational age and birth year were randomly selected. Multivariable logistic regression was used to identify risk factors for SGA, with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) accounting for potential confounders and interaction terms. Results: A total of 158,405 live SGA births were identified, with 623,584 controls randomly selected. Independent risk factors for SGA included maternal age <20 years (aOR 1.68, 95% CI 1.62, 1.75); female sex in newborns (aOR 1.28, 95% CI 1.27, 1.30); socioeconomic deprivation (aOR 1.29, 95% CI 1.21, 1.38); hypertension (aOR 1.6, 95% CI 1.52, 1.67); kidney disorders (aOR 1.29, 95% CI 1.16, 1.44); thyroid disorders (aOR 1.13, 95% CI 1.09, 1.17); systemic lupus erythematosus (aOR 2.59, 95% CI 2.33, 2.89); antiphospholipid syndrome (aOR 2.08, 95% CI 1.64, 2.64); gestational hypertension (aOR 1.69, 95% CI 1.61, 1.76); pre-eclampsia (aOR 3.12, 95% CI 3.01, 3.25); and antepartum hemorrhage (aOR 1.05, 95% CI 1.03, 1.07) after adjustment for other covariates. Conclusions: SGA was associated with younger maternal age, female newborns, underlying comorbidities, and obstetric conditions. Gestational hypertension and pre-eclampsia were significant risk factors affecting infants of both sexes and all age groups and could mask the effects of maternal age and infant sex.

Association of birth weight with neuropsychological functioning in early adolescence: A retrospective cohort study.

OBJECTIVE: This study aimed to compare the neuropsychological function in early adolescence between children born small for gestational age (SGA) or large for gestational age (LGA) and those born appropriate for gestational age (AGA). METHODS: This retrospective cohort study utilized data from the Adolescent Brain Cognitive Development study in 2016-18. Children born of singleton pregnancy with complete information of birth weight and delivery week were enrolled. Their neuropsychological functioning were assessed by the brain structural magnetic resonance imaging (MRI), combined with cognitive and behavioral measurements. Linear mixed-effects models and subgroup analyses were performed. RESULTS: Among 5,922 children aged 9-11, children born SGA and LGA demonstrated similar cognitive and behavioral performances as children born AGA (P > 0.05). In the MRI measurement, brain area and volume were lower among SGA children compared to AGA children (t=-5.626, Cohen's d = 0.448, P < 0.001; t=-6.071, Cohen's d = 0.427, P < 0.001); brain area and volume were higher among LGA children compared to AGA children (t = 8.562, Cohen's d = 0.470, P < 0.001; t = 8.562, Cohen's d = 0.470, P < 0.001). Cortical thickness was of no statistical difference (P > 0.05). These associations were confirmed by sensitivity analyses and propensity score matching. CONCLUSION: Children born of SGA and LGA status were associated with altered brain area and volume structure in early adolescence.

Association between late pregnancy prehypertension and adverse outcomes among newborns of women delivered at a tertiary hospital in Eastern Uganda: a prospective cohort study.

BACKGROUND: Prehypertension during pregnancy is currently not considered as a high-risk pregnancy state in existing guidelines despite recent research correlating it with higher rates of morbidity and mortality in both the mother and the fetus. Studies on prehypertension have not been conducted in Africa despite high rates of poor neonatal outcomes. AIMS: The study aimed to determine the association between late pregnancy prehypertension and adverse outcomes in newborns of women with late pregnancy prehypertension at Jinja Regional Referral Hospital. METHODS AND MATERIALS: Between September 2022 and January 2023, a hospital-based prospective cohort study including 300 pregnant women was conducted. Participants were divided according to third-trimester blood pressure, as determined by the JNC-8 criteria. Following hospital admission for labor and delivery, 150 normotensive women and 150 prehypertensive women were identified and followed until delivery, and their neonates were followed until death or hospital discharge. A p value of ≤ 0.05 was the threshold for statistical significance when comparing the groups using the relative risk, X2, and Mantel-Haenszel adjustment. RESULTS: Composite adverse neonatal outcomes were more common in prehypertensive women compared to normotensive women (48.67% versus 32.67%), particularly Small-for-Gestation Age (SGA), stillbirth, and composite adverse neonatal outcomes had significantly higher likelihood, with aRRs of 1.63 (95% CI 1.10-2.42, p = 0.037), 9.0 (95% CI 1.15-70.16, p = 0.010), and 1.55 (95% CI 1.16-2.08, p < 0.001), respectively. By a linear model, birthweight decreased by 45.1 g for every 10 mmHg rise in systolic blood pressure (p = 0.041, Pearson correlation of -0.118). CONCLUSION AND RECOMMENDATIONS: Prehypertension in late pregnancy increased risks for adverse neonatal outcomes, thus a need to potentially lower pregnancy hypertension cut-off levels possibly through adopting the ACC/AHA blood pressure definitions for pregnant women.

Somapacitan in Children Born SGA: 52-week Efficacy, Safety, and IGF-I Response Results from the Phase 2 REAL5 Study.

CONTEXT: Somapacitan, a once-weekly reversible albumin-binding GH derivative, is evaluated in short children born small for gestational age (SGA). OBJECTIVE: Evaluate efficacy, safety, tolerability as well as total and bioactive insulin-like growth factor-I (IGF-I) response of once-weekly somapacitan compared to daily GH in children born SGA. METHODS: REAL5 is a randomized, multi-center, open-label, controlled phase 2 study comprising a 26-week main phase, 26-week extension, and an ongoing 4-year safety extension (NCT03878446). SETTING: Thirty-eight sites across 12 countries. PATIENTS: Sixty-two GH-treatment-naïve, prepubertal short children born SGA were randomized; 61 completed 52-weeks of treatment. INTERVENTIONS: Patients randomized (1:1:1:1:1) to somapacitan (0.16, 0.20 or 0.24 mg/kg/week) or daily GH (0.035 or 0.067 mg/kg/day), all administered subcutaneously. RESULTS: Estimated mean height velocity (HV; cm/year) at week 52 was 8.5, 10.4 and 10.7 cm/year for somapacitan 0.16, 0.20 and 0.24 mg/kg/week, respectively, and 9.3 and 11.2 cm/year for daily GH 0.035 and 0.067 mg/kg/day, respectively. Dose-dependent increases in total IGF-I as well as peak IGF-I bioactivity were observed for both treatments and were similar between comparator groups. For somapacitan, exposure-response modelling indicated highest efficacy with 0.24 mg/kg/week after 52 weeks of treatment. Similar safety and tolerability were demonstrated across all groups. CONCLUSIONS: A sustained dose-dependent growth response was demonstrated for somapacitan after 52 weeks of treatment. Overall, somapacitan 0.24 mg/kg/week provides similar efficacy, safety, and tolerability, as well as comparable bioactive and total IGF-I response, as daily GH (0.067 mg/kg/day) in children born SGA.

Evaluation of sonographic and clinical measures in early versus late third trimester for birth weight prediction.

OBJECTIVE: To evaluate the optimal timing for fetal weight estimation during the third trimester. METHODS: This retrospective cohort study involved fetal weight estimations from both early (28+0-36+6 weeks) and late (37+0 weeks and beyond) third trimester. These estimations were converted to predicted birth weights using the gestation-adjusted projection formula. Birth weight predictions were compared with actual birth weights, to identify the most effective timing for weight prediction. RESULTS: The study included 3549 cases, revealing mean percentage errors (MPE) of -3.69% for early sonographic assessments, -2.5% for late sonographic assessments, and -1.9% for late clinical assessments. A significant difference was found between early and late sonographic estimations (P < 0.001), whereas late sonographic and clinical assessments did not differ significantly (P = 0.771). Weight predictions for fetuses below the 10th and above the 90th centiles were less accurate than for those within the 10th-90th centiles (P < 0.001). In women with obesity, late clinical estimations were less precise (MPE of -5.85) compared with non-obese women (MPE of -1.66, P < 0.001). For women with diabetes, early sonographic estimations were more accurate (MPE of -1.31) compared with non-diabetic patients (MPE of -3.94, P < 0.001) though this difference did not persist later in pregnancy. CONCLUSION: Sonographic and clinical weight predictions in the late third trimester were more accurate than earlier third-trimester sonographic assessments, hence continuous follow up and assessments closer to term are important. In women with diabetes, no adjustments in weight prediction methods are necessary. Accurately predicting birth weights for abnormally small or large fetuses remains challenging, indicating the need for improved screening and diagnostic strategies.

Association between interpreter use and small for gestational age infants: Interpreter use and small for gestational age in non-English speaking patients.

BACKGROUND: Limited English proficiency is associated with worse health outcomes regardless of health literacy. Prior research suggests that using interpreter services for low English proficiency helps mitigate the language barrier, is associated with improved health outcomes, and patient satisfaction; however, obstetric and neonatal outcomes and pregnancy risks in this population are not well studied. OBJECTIVES: The primary purpose of this study was to determine if low English proficiency is an independent risk factor for small for gestational age infants by utilizing interpreter use as a proxy for low English proficiency. Due to the known challenges in communication with a language barrier and discrimination against people whose first language is not English, we hypothesized that this could result in an increase in high risk conditions in pregnancy such as SGA. Our hypothesis was that the need for an interpreter would be associated with having small for gestational age infants. STUDY DESIGN: We performed a retrospective cohort study at a single center using data between 1/1/2016 and 12/31/2021; we included singleton, live births ≥21 weeks gestation. We excluded multiple gestations, intrauterine fetal demise, and delivery <21 weeks. The primary outcome was rate of small for gestational age. Small for gestational age was defined as birthweight < 10th percentile for gestational age using the 2018 Fenton newborn growth curve. Multivariable logistic regression was performed to control for confounding variables. RESULTS: Of the 26,260 patients included in the study, 71.3% were non-Hispanic White, 9.5% were Hispanic/Latino, and 7.9% were non-Hispanic Black. Overall, 1,662 (6.3%) patients utilized an interpreter. Over half (58.0%) of patients requesting interpreter services were Hispanic. In unadjusted analyses, the rate of small for gestational age was not different between patients who used interpreter services (n = 106, 6.4%) and those who did not (n = 1612, 6.6 %), p = 0.779. After adjusting for race/ethnicity, gravidity, gestational age, private insurance, diabetes, hypertension, and pre-pregnancy body mass index, the use of interpreter services was associated with decreased odds of small for gestational age (aOR 0.67, 95% CI 0.53 - 0.84). CONCLUSIONS: Our findings suggest that use of an interpreter is associated with a lower incidence of small for gestational age when controlling for patient characteristics and social determinants of health. Additional research is required to explore this association, but our results indicate that recognizing demographic risk factors and providing patients with social resources such as access to interpreter services may positively impact obstetric and neonatal outcomes.

Effects of long-term treatment with recombinant growth hormone on growth outcome in children born small for gestational age: a systematic review.

Children born small for gestational age (SGA) are defined as those having birth weight and/or length below -2 SD for gestational age. In approximately 90% of cases, SGA children experience catch-up growth in the first two years of life and a subsequent regular growth rate, reaching normal adult height. However, in the remaining 10% of cases, SGA children fail to have catch-up growth, showing persistent short stature and a constantly impaired growth rate, leading to decreased adult height compared with both general population and their mid-parental height. Therefore, in these children GH treatment may be indicated to improve growth outcome. As it can be started in most countries from the age of 4 years and is usually recommended until the completion of puberty, long-term GH treatment in SGA children (namely, longer than three years) showed a persistent improvement in height and an initial improvement in growth rate in the first year of treatment, followed by a stable, regular growth rate over time. In the present article, we systematically reviewed the currently available reports about efficacy of long-term GH treatment in SGA children, with a particular focus on growth rate over time and adult height.

Impact of isolated fetal congenital heart disease on pregnancy and perinatal outcomes.

OBJECTIVE: The aim of the present study was to evaluate the obstetric complications associated with isolated fetal congenital heart disease (CHD) by comparing pregnancies with and without this condition. METHODS: In this retrospective matched comparative study at Siriraj Hospital, Thailand, we included 233 postnatally confirmed fetal CHD cases and 466 unaffected fetuses. Controls were selected at a 2:1 ratio, ensuring that they matched the cases in terms of maternal age, parity, and history of preterm deliveries. RESULTS: Fetal CHD was significantly associated with an increased risk of spontaneous preterm labor (30% vs 9.7%; adjusted odds ratio [aOR] 2.42; 95% confidence interval [CI]: 1.35-4.36; P = 0.003), delivery before 34 gestational weeks (11.6% vs 0.6%; aOR 12.33; 95% CI: 3.32-45.78; P < 0.001), and pre-eclampsia (11.6% vs 2.8%; aOR 2.19; 95% CI: 1.01-4.76; P = 0.047). Newborns with CHD were significantly more likely to be small for gestational age (10.7% vs 5.2%; aOR 2.09; 95% CI: 1.11-3.94; P = 0.022). Intriguingly, a prenatal diagnosis of CHD was associated with a reduced risk of preterm delivery in affected pregnancies (P = 0.002). CONCLUSION: Pregnancies affected by isolated fetal CHD demonstrated a higher propensity for several adverse outcomes. These findings underscore the importance of prenatal CHD detection and tailored perinatal care to potentially improve both pregnancy outcomes and neonatal health.

Genetic Disorders and their Association with Morbidity and Mortality in Early Preterm Small for Gestational Age Infants.

BACKGROUND: Early preterm (< 34 weeks gestation) small for gestational age infants (< 10th percentile birth weight for sex and gestational age) experience high rates of morbidity and mortality, the causes of which are poorly understood. Mounting evidence suggests that genetic disorders contribute. Scarce data exist regarding the prevalence of genetic disorders and their contribution to morbidity and mortality. OBJECTIVE: This study aimed to determine the proportion of genetic disorders in early preterm small for gestational age infants (with and without congenital anomalies) compared to early preterm appropriate for gestational age infants and the association of genetic disorders with morbidity or mortality. STUDY DESIGN: This is a retrospective cohort study of infants delivered at 23 and 0/7 to 33 and 6/7 weeks' gestation from 2000-2020 from the Pediatrix Clinical Data Warehouse. Data included diagnosed genetic disorders and congenital anomalies, baseline characteristics, and morbidity or mortality. We excluded cases of death in the delivery room before NICU admission, multiple gestations, and cases transferred after birth or before death or discharge. RESULTS: We identified 223,431 early preterm infants, including 21,180 small for gestational age. Genetic disorders were present in 441 (2.3%) of small for gestational age infants without congenital anomalies, in 194 (10.8%) of small for gestational age infants with congenital anomalies, and in 304 (4.5%) of small for gestational age infants that experienced morbidity or mortality (with or without congenital anomalies). Trisomies 13, 18, and 21 were the most prevalent genetic disorders in these groups, together accounting for 145 small for gestational age infants without congenital anomalies, 117 small for gestational age infants with congenital anomalies, and 166 small for gestational age infants with morbidity or mortality (with or without congenital anomalies). Less prevalent genetic disorders consisted of other aneuploidy (45, X and 47, XXY), copy number variants (13q14 deletion syndrome, cri du chat syndrome, DiGeorge syndrome) and single gene disorders (cystic fibrosis, Fanconi anemia, G6PD deficiency, hemophilia, hypophosphatasia, sickle cell disease, and thalassemia). Comparatively, genetic disorders were found in 1792 (1.0%) appropriate for gestational age infants without congenital anomalies, in 572 (5.8%) appropriate for gestational age infants with congenital anomalies, and 809 (2.0%) appropriate for gestational age infants that experienced morbidity or mortality (with or without congenital anomalies). Genetic disorders were associated with an adjusted odds ratio (95% confidence interval) of 2.10 (1.89-2.33) of isolated small for gestational age and 12.84 (11.47-14.35) of small for gestational age accompanied by congenital anomalies. Genetic disorders were associated with an adjusted odds ratio of 2.24 (1.83-2.74) of morbidity or mortality. CONCLUSIONS: These findings suggest that genetic disorders are more prevalent in early preterm small for gestational age infants, particularly those with congenital anomalies. These findings also suggest that genetic disorders are associated with increased morbidity and mortality. These associations were primarily driven by trisomies 13, 18, and 21. Genetic diagnoses in this cohort were made through routine clinical care, principally via karyotype, chromosomal microarray, and single gene-testing. These findings support evolving clinical guidelines for genetic testing of small for gestational age infants. Our study is limited due to the lack of prospective, genome-wide testing.

Association between placental efficiency with anthropometry and nutritional phenotypes in full-term newborns from the 2010/2011 BRISA birth cohort

Abstract Objective: To study the association between placental efficiency with anthropometry and nutritional phenotypes in full-term newborns from a birth cohort. Method: This was a secondary cross-sectional analysis of data obtained in a cohort study (Brazilian RibeirãoPreto and São Luís Birth Cohort Studies - BRISA), whose deliveries were performed between 2010 and 2011. Standardized questionnaires were applied to mothers, and placentas and newborns were evaluated shortly after delivery. Placental efficiency was assessed using the ratio between birth weight and placental weight (BW/PW ratio); values below the lower quartile (25th percentile for gestational age) were considered to have low placental efficiency. Newborn phenotypes were small and large for gestational age, stunted and wasted, evaluated using the INTERGROWTH-21 growth standard. To identify the confounding variables theoretical model was constructed using Directed Acyclic Graphs, and unadjusted and adjusted logistic regression were performed. Placental measurements were obtained blindly from pregnancy and delivery data. Results: 723 mother-placenta-child triads were studied. 3.2 % of newborns were small-for-gestational-age (SGA), 6.5 %large-for-gestational-age (LGA), 5.7 %had stunting, and 0.27 % wasting. A significantly higher risk was found between low placental efficiency and SGA (OR 2.82;95 % CI 1.05-7.57), stunting (OR 2.23; 95 % CI 1.07-4.65), and wasting (OR 8.22; 95 % CI 1.96-34.37). No relationship was found between LGA and placental efficiency. Conclusions: Low placental efficiency was associated with increased risk for small-for-gestational-age, stunting, and wasting. Placental morphometry can provide valuable information on intrauterine conditions and neonatal health, helping to identify newborns at higher risk of future comorbidities.

Endometriosis and adverse pregnancy outcomes: A case-control study.

Background: The association between endometriosis and the outcome of pregnancy is one of the interesting topics. Endometriosis-related pain is alleviated with pregnancy; however, it is known to cause adverse outcomes in pregnancy. The main cause is systemic chronic inflammation caused by higher levels of cytokines, growth factors, and angiogenesis factors. Objective: This study aimed to clarify the relationship between endometriosis, deep endometriosis, adenomyosis, surgical treatment, and poor maternal consequences. Materials and Methods: In this case-control study, data from 250 women who gave birth in Hazrat Rasoul Akram hospital, Tehran, Iran from February 2015 to December 2019 was extracted from the hospital information system in January 2020. Participants were divided into 2 groups: 125 women with endometriosis and 125 women without endometriosis. We looked at how endometriosis affected mothers and newborn babies. Data on pregnancy, delivery, and newborns of both groups was extracted. Results: The mean age of participants was 32.74 ± 4.10 and 31.7 ± 5.53 yr in endometriosis and control group, respectively. In terms of pregnancy complications, placenta previa, placenta accreta, placenta abruption, pre-eclampsia, gestational diabetes mellitus, and postpartum hemorrhage remarkably increased in the endometriosis group compared to the control group. Small for gestational age was significantly higher in rectal endometriosis than women without rectal endometriosis (p = 0.03). The neonatal intensive care unit admission rate was notably higher in infants of the endometriosis group compared to controls (40.7% vs. 24.8%, p = 0.009). Conclusion: Our findings showed women with endometriosis are at a higher risk for important adverse maternal outcomes.

Can the neutrophil-to-lymphocyte ratio be used as an early marker of small fetuses for gestational age? A prospective study.

Background: Small-for-gestational-age (SGA) fetuses are at increased risk of mortality and morbidity, and less than 30% will be detected by any ultrasound scan within 4 weeks before delivery. Our aim was to evaluate the relationship between neutrophil/lymphocyte ratio (NLR) in the first trimester of pregnancy and SGA fetuses. Method: We performed a prospective study between June 2021 and August 2022, to evaluate the relationship between the neutrophil to lymphocyte ratio in maternal blood in the first trimester of pregnancy, with the birth of an SGA fetus. One hundred ninety-four participants with singleton pregnancies between 11 + 1 and 13 + 6 weeks of gestation were recruited. Pregnancies affected with diagnosed fetal chromosomal abnormalities, or chronic pathologies were excluded. SGA was defined as birthweight less than the 10th centile (N = 42) and severe SGA as birthweight less than the 3rd centile for gestation (N = 10) according to a locally derived descriptive charts. The NLR value measured in the first trimester was compared between these two groups and controls. Results: We found no statistically significant difference in NLR, (3.5 +/-1.2 vs. 3.4+/-1.2, p-value of 0.78) when comparing the SGA less than the 10th centile group to the control group. NLR was also not different between severe SGA and controls (3.6+/-1.4 vs. 3.4+/-1.2 p-value of 0.78). Conclusion: We found no association between first-trimester NLR ratio and SGA.

Plasma Vitamin D Levels Among Nigerian Mothers and their Preterm Infants.

OBJECTIVES: Preterm delivery abruptly separates a baby from the placental supply of nutrients which are mostly accreted during the third trimester. The study aimed to determine the relationship between plasma levels of vitamin D in mothers and their preterm infants within the first 24 hours of life in a Nigerian population and how this is related to the intrauterine growth pattern. METHODS: This hospital-based panel study of 121 preterm infants and their mothers was carried out in three neonatal units in southwest Nigeria. The plasma levels of vitamin D were assayed in mothers and their corresponding singleton infants while anthropometric parameters of the babies were also recorded. RESULTS: The prevalence of low plasma Vitamin D was 33.1% in the mothers and 43.8% in their preterm neonates. Plasma vitamin D levels in infants showed a moderately strong positive correlation with maternal plasma levels at birth (r = 0.517; p < 0.001). Mean maternal plasma Vitamin D was lowest in mothers whose babies were small for gestational age. CONCLUSION: Notably high proportions of Nigerian preterm infants and their mothers had low plasma Vitamin D around the period of birth and low maternal vitamin D is associated with delivery of small-for-gestational-age babies. Supplementation of Vitamin D in pregnant women and preterm babies is recommended.

OBJECTIFS: L'accouchement prématuré sépare brusquement le bébé de l'apport placentaire de nutriments, principalement accumulés au cours du troisième trimestre. L'étude visait à déterminer la relation entre les niveaux plasmatiques de vitamine D chez les mères et leurs nourrissons prématurés dans les 24 premières heures de vie dans une population nigériane, ainsi que le lien avec le schéma de croissance intra-utérin. MÉTHODES: Cette étude de panel hospitalière portant sur 121 nourrissons prématurés et leurs mères a été réalisée dans trois unités néonatales du sud-ouest du Nigeria. Les niveaux plasmatiques de vitamine D ont été dosés chez les mères et leurs nourrissons uniques correspondants, tandis que les paramètres anthropométriques des bébés ont également été enregistrés. RÉSULTATS: La prévalence de la carence en vitamine D plasmatique était de 33,1 % chez les mères et de 43,8 % chez leurs nouveau-nés prématurés. Les niveaux plasmatiques de vitamine D chez les nourrissons présentaient une corrélation positive modérément forte avec les niveaux plasmatiques maternels à la naissance (r = 0,517 ; p < 0,001). La vitamine D plasmatique maternelle moyenne était la plus faible chez les mères dont les bébés étaient petits pour l'âge gestationnel. CONCLUSION: Des proportions notablement élevées de nourrissons prématurés nigérians et de leurs mères présentaient de faibles niveaux plasmatiques de vitamine D autour de la période de naissance, et un faible taux de vitamine D maternelle est associé à la naissance de bébés petits pour l'âge gestationnel. Une supplémentation en vitamine D chez les femmes enceintes et les bébés prématurés est recommandée. MOTS-CLÉS: Nourrisson prématuré, Vitamine D, Femmes enceintes, Petit pour l'âge gestationnel.

Factors affecting growth hormone treatment in short stature children born small for gestational age in China: a single-centre, real-world study.

PURPOSE: The study aimed to evaluate the factors influencing recombinant human growth hormone (rhGH) treatment in Chinese children with short stature born small for gestational age (SGA). METHODS: A single-centre, real-world retrospective study was conducted in short stature children born SGA in China. Outcomes were observed at 6, 12, 18, 24, 30, and 36 months. Outcome measures included height standard deviation score (HTSDS), height, growth velocity (GV), and change of HTSDS (ΔHTSDS). The study used the generalized estimating equation (GEE) to identify potential influencing factors, such as rhGH treatment duration, age at rhGH initiation, sex, 11p15 hypomethylation, GH secretion, and birth weight. A subgroup analysis was conducted to investigate the impact of 11p15 hypomethylation related to SGA or impaired GH secretion. RESULTS: Of all 101 SGA patients included in the screening, 41 were eligible for inclusion in the study. The mean age at rhGH initiation was 5.6 ± 2.4 years. The results of the GEE analysis showed a significant association between time after rhGH initiation and HTSDS, height, GV, and ΔHTSDS. GV increased after treatment, with the highest increase observed in the first six months. Additionally, the study found negative correlations between 11p15 hypomethylation and GV, as well as between birth weight and both GV and ΔHTSDS. The study found a positive correlation between impairment in GH secretion and both GV and ΔHTSDS. No statistically significant difference was observed in the comparison of GV or ΔHTSDS between the initiation age of GH treatment and 11p15 hypomethylation. After 24 and 30 months of rhGH treatment, patients with impaired GH secretion had significantly higher ΔHTSDS scores. CONCLUSIONS: In short stature Chinese children born SGA, those without SGA-related 11p15 hypomethylation or with impaired GH secretion showed better response to rhGH treatment. These findings highlight the importance of pre-treatment evaluation, including genetic and endocrine assessments.

Evaluation of transplacental maternal SARS-CoV-2 antibody transfer in small for gestational age infants.

Little is known about the potential benefits of maternal immunization in the setting of high-risk pregnancies resulting in small-for-gestational-age (SGA) infants. This study compares transplacental transfer of maternal SARS-CoV-2 anti-Spike antibody in pregnancies with SGA compared to appropriate-for-gestational-age infants.

Metformin and small for gestational age babies: findings of a randomised placebo-controlled clinical trial of metformin in gestational diabetes (EMERGE).

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes because of suboptimal glucose management and glucose control and excessive weight gain. Metformin can offset these factors but is associated with small for gestational age (SGA) infants. We sought to identify risk factors for SGA infants, including the effect of metformin exposure on SGA status. METHODS: In this prespecified secondary analysis of the EMERGE trial, which evaluated the effectiveness of metformin vs placebo in treating GDM and found reduced gestational weight gain and longer time to insulin initiation with metformin use, we included women with a live-born infant and known infant birthweight and gestational age at delivery. We compared the numbers of SGA infants in both groups and explored baseline predictive factors to help identify those at highest risk of delivering an SGA infant. RESULTS: Baseline maternal characteristics were similar between SGA and non-SGA pregnancies. On multivariable-adjusted regression, no baseline maternal variables were associated with SGA status. Mothers of SGA infants were more likely to develop pre-eclampsia or gestational hypertension (18.2% vs 2.0%, p=0.001; 22.7% vs 5.4%, p=0.005, respectively); after multivariable adjustment, pre-eclampsia was positively associated with SGA status). Among SGA pregnancies, important perinatal outcomes including preterm birth, Caesarean delivery and neonatal care unit admission did not differ between the metformin and placebo groups (20.0% vs 14.3%, p=1.00; 50.0% vs 28.6%, p=0.25; 13.3% vs 42.9%, p=0.27, respectively). CONCLUSIONS/INTERPRETATION: Pre-eclampsia was strongly associated with SGA infants. Metformin-exposed SGA infants did not display a more severe SGA phenotype than infants treated with placebo. TRIAL REGISTRATION: Clinical Trials.gov NCT02980276; EudraCT number: 2016-001644-19.

Obstetric Outcomes in Women on Lithium: A Systematic Review and Meta-Analysis.

Background/Objectives: Lithium taken during pregnancy was linked in the past with increased risk for foetal/newborn malformations, but clinicians believe that it is worse for newborn children not to treat the mothers' underlying psychiatric illness. We set to review the available evidence of adverse foetal outcomes in women who received lithium treatment for some time during their pregnancy. Methods: We searched four databases and a register to seek papers reporting neonatal outcomes of women who took lithium during their pregnancy by using the appropriate terms. We adopted the PRISMA statement and used Delphi rounds among all the authors to assess eligibility and the Cochrane Risk-of-Bias tool to evaluate the RoB of the included studies. Results: We found 28 eligible studies, 10 of which met the criteria for inclusion in the meta-analysis. The studies regarded 1402 newborn babies and 2595 women exposed to lithium. Overall, the systematic review found slightly increased adverse pregnancy outcomes for women taking lithium for both the first trimester only and any time during pregnancy, while the meta-analysis found increased odds for cardiac or other malformations, preterm birth, and a large size for gestational age with lithium at any time during pregnancy. Conclusions: Women with BD planning a pregnancy should consider discontinuing lithium when euthymic; lithium use during the first trimester and at any time during pregnancy increases the odds for some adverse pregnancy outcomes. Once the pregnancy has started, there is no reason for discontinuing lithium; close foetal monitoring and regular blood lithium levels may obviate some disadvantages of lithium administration during pregnancy.

Placental lesions in systemic lupus erythematosus pregnancies associated with small for gestational age infants.

OBJECTIVES: Up to a quarter of pregnant individuals with systemic lupus erythematosus (SLE) have small for gestational age (SGA) infants. We aimed to characterize placental pathology associated with SGA infants in SLE. METHODS: We retrospectively analyzed SLE deliveries with placental analysis at UCSD from 11/2018-10/2023, comparing SLE pregnancies resulting in SGA to those that did not, and additionally, to matched pregnancies with SGA but without SLE. RESULTS: Placental analysis was available only for 28/70 (40%) SLE deliveries, which had high rates of adverse outcomes (75%). All exhibited at least one histopathologic abnormality. Key findings distinguishing 12 SLE placentas resulting in SGA infants (vs.16 without) included small placental disc for gestational age (100% vs 56%, p= 0.01), placental disc infarct (50% vs 6%, p= 0.02), and increased perivillous fibrin deposition (PVFD, 58% vs 0%, p= 0.001). All seven SLE placentas with increased PVFD resulted in SGA infants. Compared with matched non-SLE pregnancies with SGA (n = 36), the only distinguishing placental lesion was a higher prevalence of increased PVFD in SLE-associated SGA (58% vs 22%, p= 0.03). CONCLUSION: The higher prevalence of increased PVFD in placentas of SLE-associated SGA may indicate a specific mechanism of placental injury leading to SGA in this context. Thus, its presence, particularly in context of SGA, should prompt providers to screen for an underlying autoimmune disease, including SLE. Systematic placental examination in context of SLE and associated autoimmune diseases could help evaluate responses to existing therapies, comparative studies of novel therapies, and correlation to adverse outcomes.