Intrauterine Growth Restriction: Need to Improve Diagnostic Accuracy and Evidence for a Key Role of Oxidative Stress in Neonatal and Long-Term Sequelae.

Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated weight below the third percentile) and can also be present in fetuses and neonates with weights above the tenth percentile. There is a need to differentiate between IUGR and SGA whenever possible, as IUGR in particular is associated with greater perinatal morbidity, prematurity and mortality, as well as an increased risk for diseases in later life. Recognizing fetuses and newborns being "at risk" in order to monitor them accordingly and deliver them in good time, as well as to provide adequate follow up care to ameliorate adverse sequelae is still challenging. This review article discusses approaches to differentiate IUGR from SGA and further increase diagnostic accuracy. Since adverse prenatal influences increase but individually optimized further child development decreases the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood. Moreover, we present current concepts of pathophysiology, with a focus on oxidative stress and consecutive inflammatory and metabolic changes as key molecular mechanisms of adverse sequelae, and look at future scientific opportunities and challenges. Most importantly, awareness needs to be raised that pre- and postnatal care of IUGR neonates should be regarded as a continuum.

Echocardiographic assessment of brain sparing in small-for-gestational age infants and association with neonatal outcomes.

Brain sparing is an adaptive phenomenon (redistribution of blood flow to the brain) observed in fetuses exposed to chronic hypoxia, who are at risk of intrauterine growth restriction. Here, we assessed the blood flow distribution during the early neonatal period (< 7 days of life) using echocardiography, and evaluated the impact of brain-sparing on postnatal course and neurodevelopmental outcomes. This retrospective study included 42 small-for-gestational age (SGA) infants [further classified into asymmetric SGA (a-SGA, n = 21) and symmetric SGA (s-SGA, n = 21) groups according to their birth head circumference percentiles], and 1: 2 matched appropriate-for-gestational age (AGA) infants (n = 84) admitted to the neonatal intensive care unit. Left ventricular (LV) stroke volume, LV cardiac output (LVCO), upper body blood flow (UBBF), and UBBF/LVCO ratio (%) were significantly higher in both a-SGA and s-SGA infants than in AGA infants. Both a-SGA and s-SGA groups consisted predominantly of infants with higher UBBF/LVCO (%). A UBBF/LVCO ≥ 58.2% (3rd interquartile range) was associated with a later need for rehabilitative therapy after discharge. In summary, brain-sparing effect may continue during the early postnatal life in SGA infants, and may be a promising marker to detect future adverse neurodevelopmental outcomes.

Association between prenatal socioeconomic disadvantage, adverse birth outcomes, and inflammatory response at birth.

Prenatal socioeconomic disadvantage is associated with inflammation in mid- to late-life, yet whether a pro-inflammatory phenotype is present at birth and the role of adverse birth outcomes in this pathway remains unclear. We utilized data on prenatal socioeconomic disadvantage at the individual- (i.e., mother's and father's education level, insurance type, marital status, and Women, Infants, and Children benefit receipt) and census-tract level as well as preterm (< 37 weeks gestation) and small-for-gestational-age (SGA) (i.e., < 10th percentile of sex-specific birth weight for gestational age) birth status, and assessed inflammatory markers (i.e., C-reactive protein, serum amyloid p, haptoglobin, and α-2 macroglobulin) in archived neonatal bloodspots from a Michigan population-based cohort of 1000 neonates. Continuous latent variables measuring individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage were constructed and latent profile analysis was used to create a categorical inflammatory response variable (high versus low) based on continuous inflammatory marker levels. Structural equation models were used to estimate the total and direct effect of prenatal socioeconomic disadvantage on the inflammatory response at birth as well as indirect effect via preterm or SGA birth (among term neonates only), adjusting for mother's age, race/ethnicity, body mass index, smoking status, comorbidities, and antibiotic use/infection as well as grandmother's education level. There was a statistically significant total effect of both individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage on high inflammatory response among all neonates as well as among term neonates only, and a positive but not statistically significant direct effect in both groups. The indirect effects via preterm and SGA birth were both negative, but not statistically significant. Our findings suggest prenatal socioeconomic disadvantage contributes to elevated neonatal inflammatory response, but via pathways outside of these adverse birth outcomes.

The importance of the cerebroplacental ratio for the prognosis of neonatal outcome in AGA fetuses.

PURPOSE: As a Doppler sonographic parameter, the cerebroplacental ratio (CPR) provides information about fetal hemodynamics and the redistribution of fetal blood volume in response to a metabolic change. The present study was undertaken to determine the extent to which CPR can be used as a valid parameter in routine obstetric assessment. We investigated whether CPR can be used to assess the neonatal outcome in appropriate for gestational age (AGA) fetuses and its association with secondary cesarean section due to fetal distress. METHODS: In this retrospective analysis 1739 pregnant women were admitted to the University Women's Clinic Magdeburg, Germany, between January 2016 and December 2017. Of them, 710 AGA fetuses were eligible for analysis. SGA fetuses with an estimated fetal weight < 10th percentile were excluded from the study. The AGA fetuses were divided in two groups based on the CPR: 669 fetuses showed a normal CPR ≥ 1.08; 41 fetuses showed a decreased CPR < 1.08. RESULTS: In our study cohort decreased CPR in AGA fetuses was associated with threefold increased rate of cesarean sections due to fetal distress (p < 0.001). Our data suggested that low CPR is a reliable predictor of an impaired neonatal outcome in AGA fetuses in terms of a lower birth weight, transfer to neonatology, longer length of hospitalization, and the presence of severe morbidity. CONCLUSION: Decreased CPR in AGA fetuses correlated with impaired neonatal outcome and secondary cesarean section due to fetal distress. The potential role of CPR for obstetric screening should be investigated in further studies.

Childhood cardiovascular morphology and function following abnormal fetal growth.

Studies examining the link between abnormal fetal growth and cardiac changes in childhood have presented conflicting results. We studied the effect of abnormal fetal growth on cardiac morphology and function during childhood, while controlling for body size, composition and postnatal factors. We report on the follow-up of 90 children (median age 5.81 years, IQR 5.67; 5.95) born appropriate for gestational age (AGA, N = 48), small for gestational age (SGA, N = 23), or large for gestational age (LGA, N = 19); SGA and LGA defined as birth weight Z-score < - 2 and > + 2, respectively. We examined the heart using echocardiography, including Doppler and strain imaging, in relation to anthropometrics, body composition, blood pressure, physical activity, and diet. Although groupwise differences in body size decreased during the first year after birth, LGA remained larger at follow-up, with higher lean body mass and BMI, while SGA were smaller. Slight changes in left ventricular diastolic function were present in SGA and LGA, with SGA showing increased mitral diastolic E- and A-wave peak flow velocities, and increased septal E/E' ratio, and LGA showing larger left atrial volume adjusted for sex and lean body mass. In univariate analyses, lean body mass at follow-up was the strongest predictor of cardiac morphology. We found no groupwise differences at follow-up for ventricular sphericity, cardiac morphology adjusted for lean body mass and sex, or blood pressure, diet, or physical activity. Cardiac morphology is predicted by lean body mass during childhood, even in the setting of abnormal fetal growth. Our results are consistent with a limited effect of fetal programming on cardiac dimensions during childhood. Minor changes in diastolic function are present in both SGA and LGA children, however, the clinical significance of these changes at this stage is likely small.

Cardiovascular outcome of former late-onset small-for-gestational-age children at 1 year of age: CURIOSA study.

OBJECTIVE: Late-onset small-for-gestational-age (SGA) fetuses usually show normal uterine artery Doppler and were long considered to have a good peri- and postnatal outcome. Recently, these fetuses were identified to have a risk factor for cardiovascular disease. The aim of our study was to evaluate former SGA children concerning their cardiovascular risk and nutrition behavior at the age of 1 year. METHODS: We performed a prospective longitudinal cohort study at the University Hospital "Klinikum rechts der Isar" of the Technical University of Munich. Singleton pregnancies from 32 weeks with suspicion of SGA and healthy control pregnancies were included. RESULTS: A total of 100 former SGA children and 113 controls with normal weight (AGA) were examined at 1 year of age. Drop-out for 1-year follow-up was 27%. SGA children had significantly higher systolic (92.8 ± 9.8 mmHg vs. 87.5 ± 10.7 mmHg, p = 0.001), diastolic (63.1 ± 8.5 mmHg vs. 60.0 ± 10.3 mmHg, p = 0.028) and mean (73.0 ± 7.8 vs. 69.2 ± 9.7 mmHg, p = 0.004) blood pressure than AGA children. Comparing two breastfeeding periods (0-4 months vs. > 7 months), a downward trend in blood pressure values for longer breastfeeding periods was shown. CONCLUSION: Our study showed that even late-onset small-for-gestational-age fetuses seem to have cardiovascular problems, although they were previously thought to be "healthy". Up to now, blood pressure measurement is not part of indicated health checks in former SGA or even fetal growth-restricted children which should be changed. Further studies are needed to investigate cardiovascular prevention programs in children.

Higher Peripheral Cholesterol and a Positive Correlation With Risk for Large-For-Gestational-Age Neonates in Pre-Pregnancy Underweight Women.

Objective: As the high proportion of underweight pregnant women, omission of their weight gain and blood lipids management during gestation might lead to adverse pregnancy outcomes. This study aimed to determine the relationship between lipid profile and risks for adverse pregnancy outcomes in pre-pregnancy underweight women. Methods: This study was part of an ongoing cohort study including Chinese gravidas delivered from January 2015 to December 2016. Included subjects were grouped into underweight, normal-weight, and overweight by BMI before conception. Logistic regression was used to assess the association between lipid profiles during second trimester and adverse obstetric outcomes in each group. A subgroup analysis according to the gestational weight gain, in which subjects in each group were divided into above and within the Institute of Medicine (IOM) recommendations, was performed. Results: A total of 6, 223 women were included. The proportion of underweight (19.3%) was similar to that of overweight women (19.4%) in South China. Peripheral total cholesterol (TC) level in underweight women was significantly higher than that in overweight women (P <0.001). After adjusting maternal age, TC level was positively correlated to the risk for large-for-gestational-age (LGA) [aOR =2.24, 95%CI (1.08, 4.63)], and negatively related to the risk for small-for-gestational age (SGA) [aOR =0.71, 95%CI (0.59, 0.85)] in underweight women, but not in normal-weight or overweight women. The subgroup analysis showed that maternal TC level was positively correlated with the risk of LGA only in underweight women who gained weight more than the IOM recommendations. Conclusion: Underweight pregnant women with high TC levels had a higher risk for LGA, especially among women whose gestational weight gain were above the IOM recommendations. Therefore, clinical management of lipids and weight gain during gestation should also be recommended for underweight women.

Maternal smoking behaviour across the first two pregnancies and small for gestational age birth: Analysis of the SLOPE (Studying Lifecourse Obesity PrEdictors) population-based cohort in the South of England.

Maternal smoking is established to cause adverse birth outcomes, but evidence considering maternal smoking change across successive pregnancies is sparse. We examined the association between self-reported maternal smoking during and between the first two pregnancies with the odds of small for gestational age (SGA) birth (<10th percentile) in the second infant. Records for the first two pregnancies for 16791 women within the SLOPE (Studying Lifecourse Obesity PrEdictors) study were analysed. This is a population-based cohort of prospectively collected anonymised antenatal and birth healthcare data (2003-2018) in Hampshire, UK. Logistic regression was used to relate maternal smoking change to the odds of SGA birth in the second infant. In the full sample, compared to never smokers, mothers smoking at the start of the first pregnancy had higher odds of SGA birth in the second pregnancy even where they stopped smoking before the first antenatal appointment for the second pregnancy (adjusted odds ratio (aOR) 1.50 [95% confidence interval 1.10, 2.03]). If a mother was not a smoker at the first antenatal appointment for either her first or her second pregnancy, but smoked later in her first pregnancy or between pregnancies, there was no evidence of increased risk of SGA birth in the second pregnancy compared to never smokers. A mother who smoked ten or more cigarettes a day at the start of both of her first two pregnancies had the highest odds of SGA birth (3.54 [2.55, 4.92]). Women who were not smoking at the start of the first pregnancy but who subsequently resumed/began smoking and smoked at the start of their second pregnancy, also had higher odds (2.11 [1.51, 2.95]) than never smokers. Smoking in the first pregnancy was associated with SGA birth in the second pregnancy, even if the mother quit by the confirmation of her second pregnancy.

Antenatal screening of small for gestational age: Impact on obstetrical management and neonatal outcomes in case of trial of labor after 37 weeks.

OBJECTIVE: Antenatal screening of small fetuses for gestational age (SGA) is a public health challenge. The aim of this study is to assess the obstetrical management and the immediate neonatal outcomes, according to the antenatal screening of the SGA fetuses. METHODS: We performed a retrospective study in a French tertiary care hospital between January 1, 2016 and December 31, 2018. Women were eligible if they had a monofetal pregnancy with a fetus in head presentation and a trial of labor after 37 weeks. A fetus was considered SGA when the estimated fetal weight was less than the 10th percentile at the third trimester ultrasound. A newborn was considered hypotrophic when the birthweight was less than the 10th percentile. RESULTS: 8 153 newborns were included and 948 of the newborns were hypotrophic (308 were suspected for SGA, 640 were not suspected for SGA) and 7205 were eutrophic. Among the hypotrophic neonates, we observed no significant difference regarding the immediate neonatal outcomes between the two groups of fetuses suspected and not suspected for SGA. Among the fetuses not suspected for SGA, the rate of arterial umbilical cord pH below 7.10 was significantly higher in the hypotrophic newborns compared to the non hypotrophic newborns (4.7% vs 3.1%, p = 0.041). CONCLUSION: In our population, unsuspected fetal hypotrophy may be associated with an increased risk of neonatal acidosis. These results emphasize the benefit of improving prenatal screening to identify the SGA fetuses.

Intrapartum Fetal Electrocardiogram in Small- and Large-for-Gestational Age Fetuses.

OBJECTIVE: This study aimed to evaluate whether intrapartum fetal electrocardiogram (ECG) tracings with ST-elevation or depression occur more frequently in each stage of labor in small-for-gestational age (SGA) or large-for-gestational age (LGA), as compared with appropriate-for-gestational age (AGA) fetuses. STUDY DESIGN: We conducted a secondary analysis of a large, multicenter trial in which laboring patients underwent fetal ECG waveform-analysis. We excluded participants with diabetes mellitus and major fetal anomalies. Birth weight was categorized as SGA (<10th percentile), LGA (>90th percentile), or AGA (10-90th percentile) by using a gender and race/ethnicity specific nomogram. In adjusted analyses, the frequency of ECG tracings with ST-depression or ST-elevation without depression was compared according to birthweight categories and labor stage. RESULTS: Our study included 4,971 laboring patients in the first stage and 4,074 in the second stage. During the first stage of labor, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (6.7 vs. 5.5%; adjusted odds ratio [aOR]: 1.41, 95% confidence interval [CI]: 0.93-2.13), or in ST-elevation without depression (35.8 vs. 34.1%; aOR: 1.17, 95% CI: 0.94-1.46). During the second stage, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (1.6 vs. 2.0%; aOR: 0.69, 95% CI: 0.27-1.73), or in ST-elevation without depression (16.2 vs. 18.1%; aOR: 0.90, 95% CI: 0.67-1.22). During the first stage of labor, there were no differences in the frequency of ST-depression in LGA fetuses compared with AGA fetuses (6.3 vs. 5.5%; aOR: 0.97, 95% CI: 0.60-1.57), or in ST-elevation without depression (33.1 vs. 34.1%; aOR: 0.80, 95% CI: 0.62-1.03); during the second stage of labor, the frequency of ST-depression in LGA compared with AGA fetuses (2.5 vs. 2.0%, aOR: 1.36, 95% CI: 0.61-3.03), and in ST-elevation without depression (15.5 vs. 18.1%; aOR: 0.83, 95% CI: 0.58-1.18) were similar as well. CONCLUSION: The frequency of intrapartum fetal ECG tracings with ST-events is similar among SGA, AGA, and LGA fetuses. KEY POINTS: · SGA and LGA neonates are at increased risk of cardiac dysfunction.. · Fetal ECG has been used to evaluate fetal response to hypoxia.. · Fetal ST-elevation and ST-depression occur during hypoxia.. · Frequency of intrapartum ST-events is similar among SGA, AGA and LGA fetuses..

Hypertension induced by pregnancy and neonatal outcome: Results from a retrospective cohort study in preterm under 34 weeks.

OBJECTIVE: The present study seeks to assess the impact of gestational hypertensive disorders on premature newborns below 34 weeks and to establish the main morbidities and mortality in the neonatal period and at 18 months. MATERIALS AND METHODS: A retrospective observational study was carried out with 695 premature newborns of gestational age (GA) between 24 and 33 weeks and 6 days, born alive in the Neonatal ICU of Brasília's Mother and Child Hospital (HMIB), in the period from January 1, 2014, to July 31, 2019. In total, 308 infants were born to hypertensive mothers (G1) and 387 to normotensive mothers (G2). Twin pregnancies and diabetic patients with severe malformations were excluded. Outcomes during hospitalization and outcomes of interest were evaluated: respiratory distress syndrome (RDS), brain ultrasonography, diagnosis of bronchopulmonary dysplasia (BPD), diagnosis of necrotizing enterocolitis, retinopathy of prematurity, breastfeeding rate at discharge, survival at discharge and at 18 months of chronological age and relationship between weight and gestational age. RESULTS: Newborns with hypertensive mothers had significantly lower measurements of birth weight and head circumference. The G1 group had a higher risk small for gestational age (OR 2.4; CI 95% 1.6-3.6; p <0.00), as well as a greater risk of being born with a weight less than 850 g (OR 2.4; 95% CI 1.2-3.5; p <0.00). Newborns of mothers with hypertension presented more necrotizing enterocolitis (OR 2.0; CI 95% 1.1-3.7); however, resuscitation in the delivery room and the need to use surfactant did not differ between groups, nor did the length of stay on mechanical ventilation, or dependence on oxygen at 36 weeks of gestational age. Survival was better in newborns of normotensive mothers, and this was a protective factor against death (OR 0.7; 95% CI 0.5-0.9; p <0.01). In the follow-up clinic, survival at 18 months of chronological age was similar between groups, with rates of 95.3% and 92.1% among hypertensive and normotensive mothers, respectively. Exclusive breastfeeding at discharge was 73.4% in the group of hypertensive women and 77.3% in the group of normotensive mothers. There were no significant differences between groups. CONCLUSION: Among the analyzed outcomes, arterial hypertension during pregnancy can increase the risk of low weight, small babies for gestational age (SGA), deaths in the neonatal period and enterocolitis, with no differences in weight and survival at 18 months of chronological age. Arterial hypertension presents a high risk of prematurity in the neonatal period, with no difference at 18 months of age.

Exercise Capacity in Young Adults Born Small for Gestational Age.

Importance: Being born small for gestational age (SGA), approximately 10% of all births, is associated with increased risk of cardiovascular mortality in adulthood, but mechanistic pathways are unclear. Cardiac remodeling and dysfunction occur in fetuses SGA and children born SGA, but it is uncertain whether and how these changes persist into adulthood. Objective: To evaluate baseline cardiac function and structure and exercise capacity in young adults born SGA. Design, Setting, and Participants: This cohort study conducted from January 2015 to January 2018 assessed a perinatal cohort born at a tertiary university hospital in Spain between 1975 and 1995. Participants included 158 randomly selected young adults aged 20 to 40 years born SGA (birth weight below the 10th centile) or with intrauterine growth within standard reference ranges (controls). Participants provided their medical history, filled out questionnaires regarding smoking and physical activity habits, and underwent incremental cardiopulmonary exercise stress testing, cardiac magnetic resonance imaging, and a physical examination, with blood pressure, glucose level, and lipid profile data collected. Exposure: Being born SGA. Main Outcomes and Measures: Cardiac structure and function assessed by cardiac magnetic resonance imaging, including biventricular end-diastolic shape analysis. Exercise capacity assessed by incremental exercise stress testing. Results: This cohort study included 81 adults born SGA (median age at study, 34.4 years [IQR, 30.8-36.7 years]; 43 women [53%]) and 77 control participants (median age at study, 33.7 years [interquartile range (IQR), 31.0-37.1 years]; 33 women [43%]). All participants were of White race/ethnicity and underwent imaging, whereas 127 participants (80% of the cohort; 66 control participants and 61 adults born SGA) completed the exercise test. Cardiac shape analysis showed minor changes at rest in right ventricular geometry (DeLong test z, 2.2098; P = .02) with preserved cardiac function in individuals born SGA. However, compared with controls, adults born SGA had lower exercise capacity, with decreased maximal workload (mean [SD], 180 [62] W vs 214 [60] W; P = .006) and oxygen consumption (median, 26.0 mL/min/kg [IQR, 21.5-33.5 mL/min/kg vs 29.5 mL/min/kg [IQR, 24.0-36.0 mL/min/kg]; P = .02). Exercise capacity was significantly correlated with left ventricular mass (ρ = 0.7934; P < .001). Conclusions and Relevance: This cohort of young adults born SGA had markedly reduced exercise capacity. These results support further research to clarify the causes of impaired exercise capacity and the potential association with increased cardiovascular mortality among adults born SGA.

IGF1 haploinsufficiency in children with short stature: a case series.

CONTEXT: Short stature in children is a common reason for referral to pediatric endocrinologists. The underlying cause of short stature remains unclear in many cases and patients often receive unsatisfactory, descriptive diagnoses. While textbooks underline the rarity of genetic causes of growth hormone (GH) insensitivity and the severity of its associated growth failure, increased genetic testing in patients with short stature of unclear origin has revealed gene defects in the GH/insulin-like growth factor (IGF-I) axis associated with milder phenotypes. As such, heterozygous IGF1 gene defects have been reported as a cause of mild and severe short stature. Here, we aimed to describe the clinical and hormonal profile of children with IGF1 haploinsufficiency and their short-term response to growth hormone treatment (GHT). CASE DESCRIPTIONS: We describe five patients presenting with short stature, microcephaly, and in four out of five born small for gestational age diagnosed with IGF1 haploinsufficiency. The phenotype of these patients resembles that of previously described cases with similar gene defects. In our series, segregation of the short stature with the IGF1 deletion is evident from the pedigrees and our data suggests a modest response to GHT. CONCLUSIONS: This study is the first case series of complete heterozygous IGF1 deletions in children. The specific genetic defects provide a clear image of the phenotype of IGF1 haploinsufficiency - unbiased by heterozygous mutations with possible dominant negative effects on IGF-I function. We increase the evidence for IGF1 haploinsufficiency as a cause of short stature, microcephaly, and SGA.

Prevalence of small for gestational age infants in 21 cities in China, 2014-2019.

Infants who are small for gestational age (SGA) are at increased risk of neonatal and infant death, non-communicable diseases and growth retardation. However, the epidemiological characteristics of SGA remain unclear. We aim to explore the prevalence of SGA and to examine its socioeconomic associations by using data from 21 cities. 10,515,494 single live birth records between 2014 and 2019 from the Guangdong Women and Children Health Information System were included in the study. Descriptive statistical methods were used to analyze the prevalence trend of SGA and its distribution. We also analyze the associations between the prevalence of SGA and per-capita GDP. The prevalence of SGA in Guangdong Province from the years 2014-2019 was 13.17%, 12.96%, 11.96%, 12.72%, 11.45%, 11.30% respectively, and the overall prevalence was 12.28%. The prevalence of term SGA infants in Guangdong Province was 12.50%, which was much higher than that of preterm SGA (7.71%). There was a significant negative correlation between the SGA prevalence and per-capita GDP in 21 cities of Guangdong Province. The level of economic development may affect the prevalence of SGA. The prevalence of SGA in full term infants is significantly higher than in premature infants, suggesting that most SGA infants may be born at a later gestational age.

Low Birth Weight Increases the Risk of Sudden Cardiac Death in the Young: A Nationwide Study of 2.2 Million People.

Background Sudden cardiac death (SCD) constitutes a major health problem worldwide. We investigated whether birth weight (BW), small for gestational age (SGA), and large for gestational age are associated with altered risk of SCD among the young (aged 1-36 years). Methods and Results We included all people born in Denmark from 1973 to 2008 utilizing the Danish Medical Birth Register. All SCDs in Denmark in 2000 to 2009 have previously been identified. We defined 5 BW groups, SGA, and large for gestational age as exposure and SCD as the outcome. We estimated the age-specific relative risk of SCD with 95% CI. Additionally, we investigated if SGA and large for gestational age are associated with pathological findings at autopsy. The study population for the BW analyses comprised 2 234 501 people with 389 SCD cases, and the SGA and large for gestational age analyses comprised 1 786 281 people with 193 SCD cases. The relative risk for SCD was 6.69 for people with BW between 1500 and 2499 g (95% CI, 2.38-18.80, P<0.001) and 5.89 for people with BW ≥4500 g (95% CI, 1.81-19.12, P=0.003) at age 5 years. BW 2500 to 3400 g was the reference group. Compared with an appropriate gestational age, the relative risk for SGA was 2.85 (95% CI, 1.35-6.00, P=0.006) at age 10 years. For the autopsied cases, the relative risk of sudden arrhythmic death syndrome at age 5 years was 4.19 for SGA (95% CI, 1.08-16.22, P=0.038). Conclusions We found an association between BW and SCD in the young, with an increased risk among SGA infants. In addition, we found an association between SGA and sudden arrhythmic death syndrome.

Gestational systolic blood pressure trajectories and risk of adverse maternal and perinatal outcomes in Chinese women.

BACKGROUND: Associations between trajectories of systolic blood pressure (SBP) during pregnancy and pregnant outcomes remain unclear and disparate. METHODS: Data of 20,353 mothers without chronic hypertension and who delivered live singletons between January, 2014 and November, 2019, was extracted from Taicang register-based cohort. Based on SBP measured during 10 to 40 weeks of gestation, SBP trajectories were explored using latent class growth mixture model, and their associations with maternal and neonatal outcomes were assessed by logistic regression analyses. RESULTS: Six heterogeneous SBP trajectories were identified: low delayed-increasing (7.47%), low reverse-increasing (21.88%), low-stable (19.13%), medium-stable (21.64%), medium reverse-increasing (16.47%), and high stable (13.41%) trajectories. The high-stable trajectory had SBP around 125 mmHg in the 10th gestational week, and increased slightly onwards. When compared with the low-stable trajectory, the high-stable trajectory had maximally adjusted odds ratio (95% confidence interval) of 5.28 (2.76-10.10), 1.30 (1.13-1.50), 1.53 (1.12-2.08), 1.32 (1.06-1.65) and 1.64 (1.08-2.48) for gestational hypertension (GH), early-term delivery (ETD), preterm delivery (PTD), small for gestational age and low birth weight (LBW), respectively. Besides, the medium reverse-increasing trajectory showed significantly increased risk of GH and ETD, while the medium-stable trajectory had significantly elevated risk of ETD and PTD. Notably, SBP trajectories slightly but significantly improved risk discrimination of GH, ETD and LBW, over traditional risk factors. CONCLUSION: Women with different SBP trajectories were at varied risk of adverse maternal and fetal outcomes. Meanwhile, our study suggested that BP monitoring during pregnancy is necessary, especially for women with high SBP in early pregnancy or upward trajectory.

Interrupted time series study found mixed effects of the impact of the Bavarian smoke-free legislation on pregnancy outcomes.

In 2007 the German government passed smoke-free legislation, leaving the details of implementation to the individual federal states. In January 2008 Bavaria implemented one of the strictest laws in Germany. We investigated its impact on pregnancy outcomes and applied an interrupted time series (ITS) study design to assess any changes in preterm birth, small for gestational age (primary outcomes), and low birth weight, stillbirth and very preterm birth. We included 1,236,992 singleton births, comprising 83,691 preterm births and 112,143 small for gestational age newborns. For most outcomes we observed unclear effects. For very preterm births, we found an immediate drop of 10.4% (95%CI - 15.8, - 4.6%; p = 0.0006) and a gradual decrease of 0.5% (95%CI - 0.7, - 0.2%, p = 0.0010) after implementation of the legislation. The majority of subgroup and sensitivity analyses confirm these results. Although we found no statistically significant effect of the Bavarian smoke-free legislation on most pregnancy outcomes, a substantial decrease in very preterm births was observed. We cannot rule out that despite our rigorous methods and robustness checks, design-inherent limitations of the ITS study as well as country-specific factors, such as the ambivalent German policy context have influenced our estimation of the effects of the legislation.

Cardiometabolic evaluation of small for gestational age children: protective effect of breast milk / Evaluación cardiometabólica de niños pequeños para su edad gestacional: efecto protector de la leche materna

INTRODUCTION: human growth is the result of an interaction between genetic, hormonal, nutritional, and environmental factors. It is not yet fully understood what is predominant and decisive in determining an individual's weight and height. OBJECTIVE: the aim of this study was to evaluate the cardiometabolic profile of exclusively breastfed children born small for gestational age (SGA). METHODS: this is a prospective cohort study of children born at term who were classified as SGA, and as appropiate for gestational age (AGA), who were followed up to pre-school age. Anthropometric measures and body composition parameters were obtained. Breastfeeding duration was calculated in days, and achievement of catch up of weight was considered an increase in Z-score ≥ 0.67. The cardiometabolic profile was evaluated in the first month of life and repeated at pre-school age. At pre-school age, fasting blood glucose, insulin, HOMA-IR, and blood pressure were measured. RESULTS: twenty SGA and 12 AGA children were studied. The mean duration of exclusive breastfeeding (EBF) was 180 days in both groups. Of SGA children, 85 % had recovery anthropometric parameters for age within the first six months, with a speed of weight gain significantly higher than the that of AGAs (p < 0.001). SGAs continued to be thinner and smaller than AGAs at pre-school age. There was no diagnosis of overweight or obesity in the studied sample, and no differences were foun between groups in laboratory tests. CONCLUSION: these findings suggest that EBF may confer protection until pre-school age in children born SGA, who are considered at higher risk for chronic non-communicable diseases

INTRODUCCIÓN: el crecimiento humano es el resultado de la interacción de factores genéticos, hormonales, nutricionales y ambientales. Todavía no se comprende completamente lo que es predominante y decisivo para determinar el peso y la altura del individuo. OBJETIVO: el objetivo de este estudio fue evaluar el perfil cardiometabólico de niños alimentados con lactancia materna exclusivamente y que nacieron pequeños para la edad gestacional (PEG). MÉTODOS: este es un estudio de cohortes prospectivo con niños nacidos a término, unos clasificados como PEG y otros como apropiados para la edad gestacional (AEG). Se hizo un seguimiento de estos niños hasta la edad preescolar. Se realizaron medidas antropométricas y de la composición corporal. La duración de la lactancia materna se calculó en días y el éxito en la recuperación del peso se consideró como un aumento de la puntuación Z ≥ 0,67. El perfil cardiometabólico se evaluó en el primer mes de vida y se repitió en la edad preescolar. En la edad preescolar se midieron la glucosa en sangre en ayunas, la insulina, el HOMA-IR y la presión arterial. RESULTADOS: el grupo del estudio estaba formado por veinte niños PEG y doce niños AEG. La duración media de la lactancia materna exclusiva (LME) fue de 180 días en ambos grupos. De los niños PEG, el 85 % tenían parámetros antropométricos de recuperación para la edad en los primeros seis meses, siendo la velocidad del aumento de peso significativamente mayor que en los AEG (p < 0,001). Aun así, los niños PEG continuaron siendo más delgados y pequeños que los AEG en la edad preescolar. No hubo diagnóstico de sobrepeso u obesidad en la muestra estudiada, y no hay diferencia entre los grupos relativos a las pruebas de laboratorio. CONCLUSIÓN: estos hallazgos sugieren que la LME puede conferir protección hasta la edad preescolar en los niños nacidos PEG, que se consideran en mayor riesgo de contraer enfermedades crónicas no transmisibles

Effect of Correcting the Postnatal Age of Preterm-Born Children on Measures of Associations Between Infant Length-for-Age z Scores and Mid-Childhood Outcomes.

Child growth standards are commonly used to derive age- and sex-standardized anthropometric indices but are often inappropriately applied to preterm-born children (<37 weeks of gestational age (GA)) in epidemiology studies. Using the 2004 Pelotas Birth Cohort, we examined the impact of correcting for GA in the application of child growth standards on the magnitude and direction of associations in 2 a priori-selected exposure-outcome scenarios: infant length-for-age z score (LAZ) and mid-childhood body mass index (scenario A), and infant LAZ and mid-childhood intelligence quotient (scenario B). GA was a confounder that had a strong (scenario A) or weak (scenario B) association with the outcome. Compared with uncorrected postnatal age, using GA-corrected postnatal age attenuated the magnitude of associations, particularly in early infancy, and changed inferences for associations at birth. Although differences in the magnitude of associations were small when GA was weakly associated with the outcome, model fit was meaningfully improved using corrected postnatal age. When estimating population-averaged associations with early childhood growth in studies where preterm- and term-born children are included, incorporating heterogeneity in GA at birth in the age scale used to standardize anthropometric indices postnatally provides a useful strategy to reduce standardization errors.

The intra-hepatic umbilical-Porto-systemic venous shunt and fetal growth.

OBJECTIVE: The fetal liver circulation has an important role in fetal growth. The intra-hepatic Umbilical-Porto-Systemic Venous Shunt (IHUPSVS) causes a reduction of the umbilical blood flow to the liver and has been reported to have a restrictive effect on fetal growth. The aim of this study was to evaluate the effect of IHUPSVS on fetal growth. METHODS: We conducted a retrospective cohort study of IHUPSVS diagnosed between 2001 and 2019. IHUPSVS was defined as any abnormal communication between any branch of the portal vein and hepatic vein. Pre- and postnatal characteristics were collected from medical files and compared between cases with fetal growth restriction (FGR) and those appropriate for gestational age (AGA). RESULTS: Twenty-five fetuses were included in the study. Eighteen (72%) had last estimated fetal weight and birth weight below the 10th centile, four (16%) of them between the third and fifth centile, and 11 (44%) below the third centile. Median gestational age at delivery was lower for FGR than AGA fetuses (37 vs. 38 weeks, p = 0.034) and rate of preterm delivery was higher (38.9 vs. 14.3, P = 0.24). Four cases had associated structural anomalies (2 in each group), and two had minor genetic aberrations (1 in each group). CONCLUSIONS: Growth restriction is prevalent in fetuses with IHUPSVS, suggesting that fetal growth should be monitored. In equal measure, in cases with growth restriction, especially without other apparent cause, an intrahepatic shunt should be looked for.