Water Fluoridation and Birth Outcomes in California.

BACKGROUND: There is a lack of research on the relationship between water fluoridation and pregnancy outcomes. OBJECTIVES: We assessed whether hypothetical interventions to reduce fluoride levels would improve birth outcomes in California. METHODS: We linked California birth records from 2000 to 2018 to annual average fluoride levels by community water system. Fluoride levels were collected from consumer confidence reports using publicly available data and public record requests. We estimated the effects of a hypothetical intervention reducing water fluoride levels to 0.7 ppm (the current level recommended by the US Department of Health and Human Services) and 0.5 ppm (below the current recommendation) on birth weight, birth-weight-for-gestational age z-scores, gestational age, preterm birth, small-for-gestational age, large-for-gestational age, and macrosomia using linear regression with natural cubic splines and G-computation. Inference was calculated using a clustered bootstrap with Wald-type confidence intervals. We evaluated race/ethnicity, health insurance type, fetal sex, and arsenic levels as potential effect modifiers. RESULTS: Fluoride levels ranged from 0 to 2.5 ppm, with a median of 0.51 ppm. There was a small negative association on birth weight with the hypothetical intervention to reduce fluoride levels to 0.7 ppm [-2.2g; 95% confidence interval (CI): -4.4, 0.0] and to 0.5 ppm (-5.8g; 95% CI: -10.0, -1.6). There were small negative associations with birth-weight-for-gestational-age z-scores for both hypothetical interventions (0.7 ppm: -0.004; 95% CI: -0.007, 0.000 and 0.5 ppm: -0.006; 95% CI: -0.013, 0.000). We also observed small negative associations for risk of large-for-gestational age for both the hypothetical interventions to 0.7 ppm [risk difference (RD)=-0.001; 95% CI: -0.002, 0.000 and 0.5 ppm (-0.001; 95% CI: -0.003, 0.000)]. We did not observe any associations with preterm birth or with being small for gestational age for either hypothetical intervention. We did not observe any associations with risk of preterm birth or small-for-gestational age for either hypothetical intervention. CONCLUSION: We estimated that a reduction in water fluoride levels would modestly decrease birth weight and birth-weight-for-gestational-age z-scores in California. https://doi.org/10.1289/EHP13732.

Adverse Pregnancy Outcomes and Subsequent First-Time Use of Psychiatric Treatment Among Fathers in Denmark.

Importance: Becoming a first-time parent is a major life-changing event and can be challenging regardless of the pregnancy outcome. However, little is known how different adverse pregnancy outcomes affect the father's risk of psychiatric treatment post partum. Objective: To examine the associations of adverse pregnancy outcomes with first-time psychiatric treatment in first-time fathers. Design, Setting, and Participants: This nationwide cohort study covered January 1, 2008, to December 31, 2017, with a 1-year follow-up completed December 31, 2018. Data were gathered from Danish, nationwide registers. Participants included first-time fathers with no history of psychiatric treatment. Data were analyzed from August 1, 2022, to February 20, 2024. Exposures: Adverse pregnancy outcomes including induced abortion, spontaneous abortion, stillbirth, small for gestational age (SGA) and not preterm, preterm with or without SGA, minor congenital malformation, major congenital malformation, and congenital malformation combined with SGA or preterm compared with a full-term healthy offspring. Main Outcomes and Measures: Prescription of psychotropic drugs, nonpharmacological psychiatric treatment, or having a psychiatric hospital contact up to 1 year after the end of the pregnancy. Results: Of the 192 455 fathers included (median age, 30.0 [IQR, 27.0-34.0] years), 31.1% experienced an adverse pregnancy outcome. Most of the fathers in the study had a vocational educational level (37.1%). Fathers experiencing a stillbirth had a significantly increased risk of initiating nonpharmacological psychiatric treatment (adjusted hazard ratio [AHR], 23.10 [95% CI, 18.30-29.20]) and treatment with hypnotics (AHR, 9.08 [95% CI, 5.52-14.90]). Moreover, fathers experiencing an early induced abortion (≤12 wk) had an increased risk of initiating treatment with hypnotics (AHR, 1.74 [95% CI, 1.33-2.29]) and anxiolytics (AHR, 1.79 [95% CI, 1.18-2.73]). Additionally, late induced abortion (>12 wk) (AHR, 4.46 [95% CI, 3.13-6.38]) and major congenital malformation (AHR, 1.36 [95% CI, 1.05-1.74]) were associated with increased risk of nonpharmacological treatment. In contrast, fathers having an offspring being born preterm, SGA, or with a minor congenital malformation did not have a significantly increased risk of any of the outcomes. Conclusions and Relevance: The findings of this Danish cohort study suggest that first-time fathers who experience stillbirths or induced abortions or having an offspring with major congenital malformation had an increased risk of initiating pharmacological or nonpharmacological psychiatric treatment. These findings further suggest a need for increased awareness around the psychological state of fathers following the experience of adverse pregnancy outcomes.

Comparison of growth patterns in the first year of life between term small for gestational age and appropriate for gestational age South Indian infants.

BACKGROUND: Early life growth trajectories of Indian small for gestational age (SGA) infants are sparse. This study aimed to compare longitudinal growth in appropriate for gestational age (AGA) and SGA infants during their first year of life. METHODS: Apparently healthy term infants (52 SGA, 154 AGA) were recruited at birth and followed up till 1 year. Parental, sociodemographic characteristics and feeding patterns were recorded. Anthropometric measurements were assessed at birth, 3, 6, 9 and 12 months of age; Z scores and growth velocity at 3-month intervals were computed. Longitudinal measurements were compared between the two groups, using the two-way Friedmans test. Median regression with mixed effects was used to adjust covariates; p value <0.05 was considered statistically significant. RESULT: AGA infants had significantly higher median weight (kg) (2.87 (2.67, 3.04) vs 2.39 (2.25, 2.54)) at birth, (7.08 (6.50, 7.54) vs 6.49 (6.13, 6.78)) at 6 months, (8.64 (7.92, 9.14) vs 7.90 (7.36, 8.54)) at 12 months, median length (cm) ((48.10 (47.20, 49.30) vs 46.75 (45.43, 47.50)) at birth, (65.50 (64.23, 66.98) vs 63.33 (62.26, 65.28)) at 6 months, (73.30 (71.58, 74.66) vs 71.55 (70.00, 73.30)) at 12 months. SGA infants had comparable weight velocity at all intervals except 9-12 months (6.62 (6.45, 6.79) vs (6.70 (6.51, 6.85)), being significantly higher than AGA infants. Differences in skinfold thicknesses between groups were observed only at birth. Exclusivity of breast feeding was significantly higher at 3 months in AGA, compared to SGA infants (80.9% vs 57.8%). Length velocity was comparable at all ages between groups. Sexual dimorphism was observed in the growth velocities of both groups. CONCLUSION: SGA infants grew in parallel to AGA infants, having significantly lower anthropometric measurements at all time points. However, growth velocities were similar; SGA infants had significantly higher weight velocity from 9 to 12 months. Longitudinal studies beyond 1 year of age, using body composition are needed to determine the quality of growth in Indian infants.

Impact of low-dose aspirin exposure on obstetrical outcomes: a meta-analysis.

OBJECTIVE: To assess the impact of low-dose aspirin (LDA) on obstetrical outcomes through a meta-analysis of placebo-controlled randomized controlled trials (RCTs). METHODS: A systematic search of the PubMed, Cochrane Library, Web of Science and Embase databases from inception to January 2024 was conducted to identify studies exploring the role of aspirin on pregnancy, reporting obstetrical-related outcomes, including preterm birth (PTB, gestational age <37 weeks), small for gestational age (SGA), low birth weight (LBW, birthweight < 2500g), perinatal death (PND), admission to the neonatal intensive care unit (NICU), 5-min Apgar score < 7 and placental abruption. Relative risks (RRs) were estimated for the combined outcomes. Subgroup analyses were performed by risk for preeclampsia (PE), LDA dosage (<100 mg vs. ≥100 mg) and timing of onset (≤20 weeks vs. >20 weeks). RESULTS: Forty-seven studies involving 59,124 participants were included. Compared with placebo, LDA had a more significant effect on low-risk events such as SGA, PTB and LBW. Specifically, LDA significantly reduced the risk of SGA (RR = 0.91, 95% CI: 0.87-0.95), PTB (RR = 0.93, 95% CI: 0.89-0.97) and LBW (RR = 0.94, 95% CI: 0.89-0.99). For high-risk events, LDA significantly lowered the risk of NICU admission (RR = 0.93, 95% CI: 0.87-0.99). On the other hand, LDA can significantly increase the risk of placental abruption (RR = 1.72, 95% CI: 1.23-2.43). Subgroup analyses showed that LDA significantly reduced the risk of SGA (RR = 0.86, 95% CI: 0.77-0.97), PTB (RR = 0.93, 95% CI: 0.88-0.98) and PND (RR = 0.65, 95% CI: 0.48-0.88) in pregnant women at high risk of PE, whereas in healthy pregnant women LDA did not significantly improve obstetrical outcomes, but instead significantly increased the risk of placental abruption (RR = 5.56, 95% CI: 1.92-16.11). In pregnant women at high risk of PE, LDA administered at doses ≥100 mg significantly reduced the risk of SGA (RR = 0.77, 95% CI: 0.66-0.91) and PTB (RR = 0.56, 95% CI: 0.32-0.97), but did not have a statistically significant effect on reducing the risk of NICU, PND and LBW. LDA started at ≤20 weeks significantly reduced the risk of SGA (RR = 0.76, 95% CI: 0.65-0.89) and PTB (RR = 0.56, 95% CI: 0.32-0.97). CONCLUSIONS: To sum up, LDA significantly improved neonatal outcomes in pregnant women at high risk of PE without elevating the risk of placental abruption. These findings support LDA's clinical application in pregnant women, although further research is needed to refine dosage and timing recommendations.

MTHFR 677 C > T Gene Polymorphism is Associated with Large for Gestational Age Infants.

BACKGROUND: The aim of this study was to investigate the methylenetetrahydrofolate reductase (MTHFR) 677 C > T gene polymorphism in term infants born small (SGA), appropriate (AGA), and large for gestational age (LGA). METHODS: The study comprised 165 newborns with SGA, LGA and AGA. Genomic DNA was isolated from the peripheral blood. Samples were genotyped for MTHFR 677 C > T gene polymorphisms using PCR-RFLP. RESULTS: There was a statistically significant difference between the genotype and their allelic distribution of AGA, SGA, and LGA. The newborns carrying the TT genotype had higher birth weight than those carrying the CC and CT genotypes. The frequency of MTHFR 677 TT genotype and T allele was significantly higher and was found to be linked with a higher risk in LGA than in the AGA group. CONCLUSIONS: The MTHFR 677 C > T gene polymorphism can be used as a genetic marker in Turkish LGA newborns, but not in SGA.

Postexchange transfusion-related acute lung injury in a term neonate.

We report a successful case where a newborn with transfusion-related acute lung injury following an exchange transfusion was effectively treated using conservative methods, eliminating the need for surfactant therapy. Very few instances of this complication have been documented globally. A low birth weight, small for gestational age, term neonate, diagnosed with hyperbilirubinaemia due to Rh incompatibility, experienced sudden respiratory distress in the form of severe retractions, tachypnoea and cyanosis 3 hours after the procedure. Neonate required mechanical ventilation on the grounds of mixed acidosis and diffuse alveolar infiltrates on the chest radiograph. The medical team suspected and treated the baby for transfusion-related acute lung injury through conservative measures. Transfusion-related acute lung injury, an acute life-threatening complication of blood component transfusion, can exhibit symptoms in neonates that are frequently misinterpreted as sepsis. The baby was discharged in good health after successful management after 19 days.

Risk of Adverse Neonatal Outcomes After Combined Prenatal Cannabis and Nicotine Exposure.

Importance: The prevalence of cannabis use in pregnancy is rising and is associated with adverse perinatal outcomes. In parallel, combined prenatal use of cannabis and nicotine is also increasing, but little is known about the combined impact of both substances on pregnancy and offspring outcomes compared with each substance alone. Objective: To assess the perinatal outcomes associated with combined cannabis and nicotine exposure compared with each substance alone during pregnancy. Design, Setting, and Participants: This retrospective population-based cohort study included linked hospital discharge data (obtained from the California Department of Health Care Access and Information) and vital statistics (obtained from the California Department of Public Health) from January 1, 2012, through December 31, 2019. Pregnant individuals with singleton gestations and gestational ages of 23 to 42 weeks were included. Data were analyzed from October 14, 2023, to March 4, 2024. Exposures: Cannabis-related diagnosis and prenatal nicotine product use were captured using codes from International Classification of Diseases, Ninth Revision, Clinical Modification, and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification. Main Outcome and Measures: The main outcomes were infant and neonatal death, infants small for gestational age, and preterm delivery. Results were analyzed by multivariable Poisson regression models. Results: A total of 3 129 259 pregnant individuals were included (mean [SD] maternal age 29.3 [6.0] years), of whom 23 007 (0.7%) had a cannabis-related diagnosis, 56 811 (1.8%) had a nicotine-use diagnosis, and 10 312 (0.3%) had both in pregnancy. Compared with nonusers, those with cannabis or nicotine use diagnoses alone had increased rates of infant (0.7% for both) and neonatal (0.3% for both) death, small for gestational age (14.3% and 13.7%, respectively), and preterm delivery (<37 weeks) (12.2% and 12.0%, respectively). Moreover, risks in those with both cannabis and nicotine use were higher for infant death (1.2%; adjusted risk ratio [ARR], 2.18 [95% CI, 1.82-2.62]), neonatal death (0.6%; ARR, 1.76 [95% CI, 1.36-2.28]), small for gestational age (18.0%; ARR, 1.94 [95% CI, 1.86-2.02]), and preterm delivery (17.5%; ARR, 1.83 [95% CI, 1.75-1.91]). Conclusions and Relevance: These findings suggest that co-occurring maternal use of cannabis and nicotine products in pregnancy is associated with an increased risk of infant and neonatal death and maternal and neonatal morbidity compared with use of either substance alone. Given the increasing prevalence of combined cannabis and nicotine use in pregnancy, these findings can help guide health care practitioners with preconception and prenatal counseling, especially regarding the benefits of cessation.

The association between ultra-processed food and common pregnancy adverse outcomes: a dose-response systematic review and meta-analysis.

OBJECTIVES: Given the increasing incidence of negative outcomes during pregnancy, our research team conducted a dose-response systematic review and meta-analysis to investigate the relationship between ultra-processed foods (UPFs) consumption and common adverse pregnancy outcomes including gestational diabetes mellitus (GDM), preeclampsia (PE), preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) infants. UPFs are described as formulations of food substances often modified by chemical processes and then assembled into ready-to-consume hyper-palatable food and drink products using flavors, colors, emulsifiers, and other cosmetic additives. Examples include savory snacks, reconstituted meat products, frozen meals that have already been made, and soft drinks. METHODS: A comprehensive search was performed using the Scopus, PubMed, and Web of Science databases up to December 2023. We pooled relative risk (RR) and 95% confidence intervals (CI) using a random-effects model. RESULTS: Our analysis (encompassing 54 studies with 552,686 individuals) revealed a significant association between UPFs intake and increased risks of GDM (RR = 1.19; 95% CI: 1.10, 1.27; I2 = 77.5%; p < 0.001; studies = 44; number of participants = 180,824), PE (RR = 1.28; 95% CI: 1.03, 1.59; I2 = 80.0%; p = 0.025; studies = 12; number of participants = 54,955), while no significant relationships were found for PTB, LBW and SGA infants. Importantly, a 100 g increment in UPFs intake was related to a 27% increase in GDM risk (RR = 1.27; 95% CI: 1.07, 1.51; I2 = 81.0%; p = 0.007; studies = 9; number of participants = 39,812). The non-linear dose-response analysis further indicated a positive, non-linear relationship between UPFs intake and GDM risk Pnonlinearity = 0.034, Pdose-response = 0.034), although no such relationship was observed for PE (Pnonlinearity = 0.696, Pdose-response = 0.812). CONCLUSION: In summary, both prior to and during pregnancy, chronic and excessive intake of UPFs is associated with an increased risk of GDM and PE. However, further observational studies, particularly among diverse ethnic groups with precise UPFs consumption measurement tools, are imperative for a more comprehensive understanding.

Per- and polyfluoroalkyl substances (PFAS) and fetal growth: A nation-wide register-based study on PFAS in drinking water.

BACKGROUND: There is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth. OBJECTIVES: We conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA). MATERIALS AND METHODS: We included all births in Sweden during 2012-2018 of mothers residing ≥ four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of ß coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture. RESULTS: Among the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01-1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight. DISCUSSIONS: We observed an association of the sum of PFAS4 - especially PFOS - with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation.

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OBJECTIVES: To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. METHODS: Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. RESULTS: A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). CONCLUSIONS: Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.

Italian neonatal birthweight charts derived from INeS not separated by birth order.

BACKGROUND: Identifying high-risk neonates with abnormal fetal growth is crucial for health risk prediction and early intervention. Small for gestational age (SGA) and large for gestational age (LGA) classifications highlight neonates having a higher risk for postnatal diseases. Accurate diagnosis depends on precise anthropometric measurements and appropriate reference data. In 2010, specific neonatal charts for Italian singletons (INeS charts) were published, tracing separately for first- and later-born neonates due to a 3% birth weight difference. We present INeS charts for birth weight non-separated by first- and later-born babies useful when information on parity is unavailable or unreliable, or for better comparisons with other neonatal charts that are not separated by birth-order. METHODS: INeS charts were traced using a parametric function. Starting with the parameters estimates published in a different paper, INeS charts not separated by birth order were traced for the gestational age range of 23 to 42 weeks. In a second step the charts were parametrized as Cole and Green Lambda Mu and Sigma (LMS) model, allowing computation of standard deviation scores. RESULTS: The centiles of non-separated INeS charts follow between first- and later-born charts. Distances varied due to changing first-born proportions with gestational age, Max differences of about 100g with later born and 70g with first-born were observed at term. S and L functions have a similar shape for boys and girls. S function shows a pick at about 29 weeks, L function has positive values in all the range of gestational age with a pick at 39 weeks. CONCLUSIONS: The study presents non-separated Birth Weight INeS charts, bridging the gap when parity information is unavailable. Differences with separated charts were generally small, making them reliable for neonatal health assessment. Insights from L and S parameters contribute to standardized birth weight and adjust it by sex and Gestational Age, useful for defining SGA or LGA neonates. The paper enhances neonatal care tools, showcasing INeS chart flexibility in different clinical scenarios and supporting neonatology research.

Long-term benefits of exclusive human milk diet in small for gestational age neonates: a systematic review of the literature.

Evidence about feeding practices' consequences in small for gestational age newborns is not well established because they are less likely to initiate and continue breastfeeding than other newborns. Our aim was to study current knowledge about the benefits of exclusive human milk diet after 2 years of age in small for gestational age newborns. A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline criteria. Pubmed and Scopus were searched for studies published from databases inception until June 2, 2023. Included articles were analysed and synthesised. Risk of bias and level of evidence assessments were performed. They were enrolled small for gestational age newborns fed by breastfeeding, breast milk or donor milk. The systematic review included 9 articles which were related to 4 health domains: neurodevelopment, cardiovascular, somatic growth and bone mineralization and atopy. Extracted data support a beneficial effect of breastfeeding on these outcomes. Better quality of evidence and longer follow-up are needed.

Small for Gestational Age Newborns in French Guiana: The Importance of Health Insurance for Prevention.

Objectives: Small for gestational age (SGA) newborns have a higher risk of poor outcomes. French Guiana (FG) is a territory in South America with poor living conditions. The objectives of this study were to describe risk factors associated with SGA newborns in FG. Methods: We used the birth cohort that compiles data from all pregnancies that ended in FG from 2013 to 2021. We analysed data of newborns born after 22 weeks of gestation and/or weighing more than 500 g and their mothers. Results: 67,962 newborns were included. SGA newborns represented 11.7% of all newborns. Lack of health insurance was associated with SGA newborns (p < 0.001) whereas no difference was found between different types of health insurance and the proportion of SGA newborns (p = 0.86). Mothers aged less than 20 years (aOR = 1.65 [1.55-1.77]), from Haiti (aOR = 1.24 [1.11-1.39]) or Guyana (aOR = 1.30 [1.01-1.68]) and lack of health insurance (aOR = 1.24 [1.10-1.40]) were associated with SGA newborns. Conclusion: Immigration and precariousness appear to be determinants of SGA newborns in FG. Other studies are needed to refine these results.

Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.

Comparative analysis of foetal and neonatal growth curves.

INTRODUCTION: Our aim was to determine which foetal or neonatal growth curves discriminate the probability of dying of newborns with low birth weight for their gestational age (small for gestational age, SGA) and sex (weight < 10th percentile) and to establish the curves that are presumably most useful for monitoring growth through age 10 years. MATERIAL AND METHODS: The analysis included every neonate (15 122) managed in our hospital (2013-2022) and all neonates born preterm before 32 weeks (6913) registered in the SEN1500 database (2019-2022). We considered most useful those curves with the highest likelihood ratio (LR) for dying with or without a history of SGA in each subgroup of gestational ages. Theoretically, the optimal curves for monitoring growth would be those with a higher R2 in the quantile regression formulas for the 50th percentile. RESULTS: The growth curves exhibiting the strongest association between SGA and hospital mortality are the Intergrowth fetal curves and the Fenton neonatal curves in infants born preterm before 32 weeks. However, the optimal curves for premature babies and neonates overall were those of Olsen and Intergrowth. The most useful curves to monitor anthropometric values alone until age 10 years of age are the longitudinal Intergrowth curves followed by the WHO standards, but if a single reference is desired from birth through age 10 years, the best option is the Fenton curves followed by the WHO standards. CONCLUSIONS: The Intergrowth reference provides the most discriminating foetal growth curves. In neonatal clinical practice, the optimal references are the Fenton followed by the WHO charts.

Late Eruption of Mandibular Central Incisor in Small for-Gestational-Age Infants: A Cohort Study.

Purpose: To evaluate the chronology of the eruption of primary mandibular central incisors in infants born preterm and with low weight (PLBW) and its association with weight/length ratio for gestational age (GA) at birth, individual characteristics and hospitalization at birth. Methods: A cohort of 46 infants was followed at a multidisciplinary reference center at a university hospital in Belo Horizonte, Brazil. The inclusion criteria were infants born preterm with low/very low/extreme low birth weight and at least four months of age. Oral clinical examinations were carried out by a calibrated dentist for a total of eight months, with a one-month interval between each examination, to verify the chrono- logy of eruption of the primary mandibular central incisors. Caregivers completed a sociodemographic and health questionnaire. Data on neonatal hospitalization were collected from medical records. Data were analyzed with the Kaplan-Meier method and log rank test, and bivariate analysis was done using the Mann-Whitney method and Kruskal-Wallis test (P <0.05). Results: The average age at eruption of primary lower central incisors was 11 months for both sexes. No association was found between tooth eruption and child hospitalization or individual characteristics (P >0.05). Infants large for gestational age had earlier tooth eruption (9.3±1.41 months) than infants small for gestational age (13.6±3.29 months; P <0.05).Conclusion: The most likely age for the eruption of the first primary teeth in infants born preterm and with low weight was 11 months, and there was no influence of individual characteristics and hospitalization at birth. Small-for-gestational age infants experienced delayed tooth eruption compared to large-for-GA infants.

Increasing Preterm Delivery and Small for Gestational Age Trends in South Carolina during the COVID-19 Pandemic.

Preterm delivery (PTD) complications are a major cause of childhood morbidity and mortality. We aimed to assess trends in PTD and small for gestational age (SGA) and whether trends varied between race-ethnic groups in South Carolina (SC). We utilized 2015-2021 SC vital records linked to hospitalization and emergency department records. PTD was defined as clinically estimated gestation less than (<) 37 weeks (wks.) with subgroup analyses of PTD < 34 wks. and < 28 wks. SGA was defined as infants weighing below the 10th percentile for gestational age. This retrospective study included 338,532 (243,010 before the COVID-19 pandemic and 95,522 during the pandemic) live singleton births of gestational age ≥ 20 wks. born to 260,276 mothers in SC. Generalized estimating equations and a change-point during the first quarter of 2020 helped to assess trends. In unadjusted analyses, pre-pandemic PTD showed an increasing trend that continued during the pandemic (relative risk (RR) = 1.04, 95% CI: 1.02-1.06). PTD < 34 wks. rose during the pandemic (RR = 1.07, 95% CI: 1.02-1.12) with a significant change in the slope. Trends in SGA varied by race and ethnicity, increasing only in Hispanics (RR = 1.02, 95% CI: 1.00-1.04) before the pandemic. Our study reveals an increasing prevalence of PTD and a rise in PTD < 34 wks. during the pandemic, as well as an increasing prevalence of SGA in Hispanics during the study period.

Improved estimation of the relationship between fetal growth and late stillbirth in the United States, 2014-15.

In the United States the rate of stillbirth after 28 weeks' gestation (late stillbirth) is 2.7/1000 births. Fetuses that are small for gestational age (SGA) or large for gestational age (LGA) are at increased risk of stillbirth. SGA and LGA are often categorized as growth or birthweight ≤ 10th and ≥ 90th centile, respectively; however, these cut-offs are arbitrary. We sought to characterize the relationship between birthweight and stillbirth risk in greater detail. Data on singleton births between 28- and 44-weeks' gestation from 2014 to 2015 were extracted from the US Centers for Disease Control and Prevention live birth and fetal death files. Growth was assessed using customized birthweight centiles (Gestation Related Optimal Weight; GROW). The analyses included logistic regression using SGA/LGA categories and a generalized additive model (GAM) using birthweight centile as a continuous exposure. Although the SGA and LGA categories identified infants at risk of stillbirth, categorical models provided poor fits to the data within the high-risk bins, and in particular markedly underestimated the risk for the extreme centiles. For example, for fetuses in the lowest GROW centile, the observed rate was 39.8/1000 births compared with a predicted rate of 11.7/1000 from the category-based analysis. In contrast, the model-predicted risk from the GAM tracked closely with the observed risk, with the GAM providing an accurate characterization of stillbirth risk across the entire birthweight continuum. This study provides stillbirth risk estimates for each GROW centile, which clinicians can use in conjunction with other clinical details to guide obstetric management.

Placentae of small appropriately-grown-for-gestational-age neonates exhibit sexually dimorphic transcriptomic changes representative of placental insufficiency.

INTRODUCTION: Previous studies have reported that neonates less than the 25th BWC especially if they were male, were more likely to be associated with birth complications suggesting small neonates often identified as appropriately grown are at risk of adverse outcomes. We have questioned whether smaller neonates not typically categorized as "small for gestational age" may not reach their genetically determined growth due to placental insufficiency. METHODS: RNA-Seq was performed on the Illumina NovaSeq 600 using term placentae from neonates that were less than the 10th birthweight centile (BWC) (n = 39), between the 10th and the 30th BWC (n = 15) or greater than the 30th BWC (n = 23). Bioinformatic analyses were conducted and statistical significance was assessed at a level of P < 0.05 for single comparisons or FDR <0.05 unless otherwise noted. RESULTS: Gene set enrichment analysis revealed differences between BWC groups and in relation to the sex of the placenta. Genes associated with hypoxia, inflammatory responses, estrogen responsive genes, and androgen responsive genes were enriched (FDR <0.1) for in placentae of neonates <10th BWC regardless of sex and also in male placentae of neonates between the 10th-30th BWC. Female placenta of neonates between the 10th-30th BWC were comparable to placentae of neonates >30th BWC. DISCUSSION: These findings provide evidence that small male neonates may be at a greater risk of an adverse outcome than females due to changes in gene expression that are associated with placental dysfunction. The current data raises questions of whether placental pathology for smaller appropriately grown neonates should be scientifically and clinically examined in more depth.