The utility of an obesity-specific small for gestational age standard for pregnancies complicated by maternal obesity*

Introduction: An obesity-specific standard for small for gestational age (SGA) pregnancies may help identify additional at risk pregnancies.

Methods: This was a retrospective cohort study of all non-anomalous singleton neonates born in Texas from 2006–2011. Analysis was limited to births between 34 and 42?weeks gestation. Two SGA birth weight standards (birth weight ≤10th centile) were generated, one using the entire population (SGA_pop) and another using obese pregnancies (SGA_cust). The outcomes of interest included: risks of stillbirth, neonatal death, 5-minute Apgar score below 7, NICU admission, and assisted ventilation?>6?h.

Results: Using the population standard, the prevalence of SGA complicated by obesity was 8.1%, compared with 10.3% using the obesity-specific standard. 10,457 additional pregnancies were identified as SGA. Compared to obese AGA pregnancies, the aHR for stillbirth was 5.45 [4.28, 6.94] for SGA_pop, and 1.21 [0.54, 2.74] for SGA_cust-pop. The risks for the following neonatal complications were slightly higher for SGA_cust-pop group compared to AGA group: neonatal death aOR 1.40 [1.05, 1.87], low 5-minute Apgar 1.31 [1.09, 1.57], and NICU admission 1.13 [1.03, 1.25]. These risks were lower than SGA_pop.

Conclusions: Using an obesity-specific SGA standard, a subgroup of pregnancies with marginally increased risk for neonatal complications was identified.     

Inadequate weight gain in obese women and the risk of small for gestational age (SGA): a systematic review and meta-analysis

Objectives: To examine the association between small for gestational age (SGA) and inadequate gestational weight gain (GWG) in obese women (compared with Institute of Medicine [IOM] guidelines) stratified by obesity classes.

Methods: We conducted a meta-analysis of original researches with sufficient information about inadequate GWG in obese women stratified by obesity classes. SGA as the chief outcome was extracted and assessed in our analysis. MEDLINE and EMBASE were searched through Ovid from 28 May 2009 to 1 December 2015. Quality was assessed using a modified Newcastle–Ottawa scale.

Results: 480 citations were screened and 13 studies (437 512 obese women) were included. Obese women who gained weight below the guidelines had higher risks of SGA than those who gained weight within the guidelines (OR 1.28; 95% CI 1.14–1.43). The same conclusions were also confirmed in Class I, Class II and Class III of obese women: Class I (OR 1.37; 95% CI 1.22–1.54); Class II (OR 1.38; 95% CI 1.24–1.54); Class III (OR 1.25; 95% CI 1.14–1.36).

Conclusions: From our analysis, the guidelines of IOM can be applied to all the classes of obesity. More accurate boundaries for each obesity class should be established to evaluate the maternal and fetal risks. Diverse populations are thus necessary for more studies in the future.     

Low first-trimester hemoglobin and low birth weight, preterm birth and small for gestational age newborns.

OBJECTIVE: To examine the relationship between first-trimester hemoglobin (Hb) concentration and risk of low birth weight (LBW), preterm birth and small for gestational age (SGA). METHODS: Data were obtained from a population-based prenatal care program in China. A total of 88,149 women who delivered during 1995-2000 and had their Hb measured in the first trimester were selected as study subjects. RESULTS: The prevalence of anemia (Hb<110 g/L) was 22.1% in the first trimester. The risk of LBW, preterm birth and SGA was increased steadily with the decrease of first-trimester Hb concentration. After controlling for confounding factors, women with Hb 80-99 g/L had significantly higher risk for LBW (OR=1.44, 95% CI 1.17-1.78), preterm birth (OR=1.34, 95% CI 1.16-1.55) and SGA (OR=1.13, 95% CI 0.98-1.31) than women with Hb 100-119 g/L. No elevated risk was noted for women with Hb> or =120 g/L. CONCLUSION: Low first-trimester Hb concentration increases the risk of LBW, preterm birth and SGA.     

Evaluation of carnitine deficit in very low birth weight preterm newborns small for their gestational age

Objective: To verify whether small-for-gestational-age (SGA) preterm newborns represent a special risk group for carnitine deficiency. Secondary outcome includes assessment of longitudinal differences of total carnitine (TC), free carnitine (FC) and acylcarnitines between SGA and appropriate-for-gestational-age (AGA).

Methods: A retrospective study to evaluate carnitine and acylcarnitines profile on 144 very-low-birth weight newborns (VLBW), classified as AGA (n?=?73) and SGA (n?=?71), was performed by tandem mass spectrometry, during their first 5 weeks of life. Carnitine deficiency was defined as FC <40?µmol/L and FC/TC <0.7.

Results: Carnitine deficiency was observed in the two study groups throughout the monitoring period (maximum FC: 36.05?µmol/L in AGA and 32.24?µmol/L in SGA). FC/TC remains under 0.7 in both with progressive improvement. Unlike expected, a comparatively higher value of TC, FC and total acylcarnitines (tAC) was found in SGA during the first 2 weeks, with significant relevance on day 3–5, especially for tAC (p?<?0.001). The only acylcarnitine with persistently lower value in SGA is C5 (p?<?0.05 in first 2 weeks).

Conclusions: A carnitine deficiency was demonstrated in all VLBW. Although birth weight restriction has been suggested as a risk factor for impaired carnitine status, in our study, SGA was not related with higher carnitine deficiency.     

Long-term cardiovascular hospitalizations of small for gestational age (SGA) offspring born to women with and without gestational diabetes mellitus (GDM)‡

Abstract

Objective: To assess whether delivery of small for gestational age (SGA) neonates to mothers with gestational diabetes mellitus (GDM) increases the risk of long-term cardiovascular offspring hospitalizations compared to SGA neonates born to mothers without GDM. Study design: This is a population-based retrospective cohort study. The study group was SGA offspring born to mothers with GDM (n?=?259), while the control group was SGA offspring born to mothers without GDM (n?=?9053). The main factor evaluated was offspring cardiovascular hospitalizations up to the age of 18?years. Kaplan-Meier survival curve was used to estimate cumulative incidence of cardiovascular hospitalizations. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (HR) for cardiovascular hospitalizations. Results: SGA children born to mothers with GDM had significantly higher rates of cardiovascular-related hospitalizations (1.9% vs. 0.7%, p?=?.026). A Kaplan-Meier survival curve demonstrated that SGA children born to GDM mothers had a higher cumulative incidence of cardiovascular hospitalizations (log-rank p?=?.037). The Cox regression model, while controlling for confounders, demonstrated that delivery of SGA neonates to mothers with GDM is independently associated with long-term cardiovascular offspring hospitalizations (adjusted HR =2.6; 95% CI 1.02–6.55 p?=?.045). Conclusion: Delivery of SGA neonates born to mothers with GDM is independently associated with long-term cardiovascular offspring hospitalizations.     

Population-based study on antenatal corticosteroid treatment in preterm small for gestational age and non-small for gestational age twin infants

Objectives: To assess the associations between antenatal corticosteroid use (ACU), mortality and severe morbidities in preterm, twin neonates and compare these between small for gestational age (SGA) and non-SGA twins.

Materials and methods: Population-based study using data collected by the Israel National Very Low Birth Weight infant database from 1995 to 2012, comprising twin infants of 24–31 weeks' gestation, without major malformations. Univariate and multivariable logistic regression analyses were performed.

Results: Among the 6195 study twin infants, 784 were SGA. Among SGA neonates, ACU were associated with decreased mortality (23.9% vs. 39.2%, p?p?=?0.0015), similar to the effect in non-SGA neonates (mortality 13.0% vs. 24.5%, p?p?P_interaction?=?0.69. Composite adverse outcome risk was also reduced in SGA (OR?=?0.78, 95% CI 0.50–1.23) and non-SGA groups (OR?=?0.78, 95% CI 0.65–0.95), P_interaction?=?0.95.

Conclusions: ACU should be considered in all mothers with twin gestation, at risk for preterm delivery at 24–31 weeks, in order to improve perinatal outcome.     

Pathological examination of the placenta in small for gestational age (SGA) children with or without postnatal catch-up growth

Background/objective: Approximately 10% of small for gestational age (SGA) infants fail to catch up. The relationship between postnatal growth and placental pathology in SGA infants remains unclear. Our aim was to assess the involvement of placental pathology in postnatal growth of SGA infants.

Methods: We retrospectively evaluated placental pathology and postnatal growth in single-pregnancy infants born after 37 gestational weeks in our institution, with both birth weight and length below ?2 standard deviation scores (SDS) of the normal weight and length. “Catch-up” was defined as height reaching ?2 SDS before the second birthday. Pathology of the placenta was classified into: abnormality due to maternal factors or fatal factors, villitis of unknown etiology (VUE), other abnormalities and no abnormality.

Results: Of the 33?084 infants, 142 met our criteria and 49 of them had analyzable data. The overall catch-up rate was 84%. Catch-up growth took place in all infants with no placental abnormality and only 57% of infants with abnormality due to fatal factors. There was no significant relationship between catch-up rate and other factors.

Conclusion: Placental pathology is associated with postnatal growth in SGA children born at term. Placental abnormality due to fetal factors is related to poor catch-up rate.     

Analysis of amino acids and acyl carnitine profiles in low birth weight,preterm, and small for gestational age neonates

Objective: To analyze the amino acids (AA) and acyl carnitine (AC) profiles in dry blood spot (DBS) specimens of low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA), and to compare the concentration difference of AA and AC with those without above.

Methods: This is a retrospectively study. Eight thousand nine hundred and seventy-nine uncomplicated pregnant newborns were enrolled into the study. DBS were collected on the third day of life, and concentrations of 11 types of AA, free carnitine and 30 types of AC were detected by using high-performance liquid chromatography tandem mass spectrometry (HPLC–MS). Shapiro–Wilk test and Kruskal–Wallis rank test were applied in statistical analysis.

Results: Concentrations of most AA and AC in infants born in SGA were significantly higher than those in non-SGA group, while lower in LBW and PTB groups than those in non-LBW and non-PTB groups (p?Conclusions: The difference of concentration of AA and AC in the subgroups suggested there may be a dysutilization of AA and AC in SGA, but an inborn insufficient of AA and AC in LBW and PTB neonates.     

Long-term endocrine outcome of small for gestational age infants born to mothers with and without gestational diabetes mellitus

Abstract

Small for gestational age (SGA) infants and infants born to mothers with gestational diabetes mellitus (GDM) are at an increased risk for significant morbidity and mortality, mainly metabolic disorders. We aimed to question the long-term endocrine morbidity of SGA infants born to mothers with GDM compared to SGA infants born to non- diabetic mothers. A population-based cohort study was performed to assess the risk for endocrine morbidity among children born SGA to mothers with and without GDM. The main outcome evaluated was endocrine morbidity of the offspring up to the age of 18 years, predefined in a set of ICD-9 codes. Endocrine morbidity included thyroid disease, insulin and non-insulin dependent diabetes mellitus, hypoglycemia, childhood obesity, parathyroid hormone disease, adrenal disease, and sex hormone disease. All SGA infants born between the years 1991 and 2014 and discharged alive from the hospital were included in the study. Multiple pregnancies, infants with congenital malformations or chromosomal abnormalities and mothers lacking prenatal care were excluded from the analysis. Kaplan–Meier survival curve was constructed to compare cumulative endocrine morbidity. A Cox proportional hazards model was conducted to control for confounders. During the study period, 9312 newborn infants met the inclusion criteria, of them 259 SGA infants were born to mothers with GDM and 9053 SGA infants were born to mother without GDM. No significant differences in long-term endocrine morbidity were noted between the groups (0.8% in children born to mothers with GDM vs. 0.5% in children born to non-diabetic mothers, p?=?.62). Likewise, the Kaplan–Meier survival curve did not demonstrate a significantly higher cumulative incidence of endocrine morbidity in offspring of women with GDM (log rank test p=.67). In a Cox regression model, while controlling for ethnicity, hypertensive disorders, preterm birth, and maternal age, delivery of an SGA neonate to mother with GDM was not associated with long-term endocrine morbidity of the offspring (adjusted HR 1.2, 95% confidence interval 0.27–5.00, p=.82). SGA infants born to mothers with GDM are not at an increased risk for long-term endocrine morbidity as compared with SGA infants born to non-diabetic mothers.     

Maternal anemia during pregnancy and small for gestational age: a systematic review and meta-analysis

Objective: Anemia is a major public health and nutritional problem in the world. Studies have reported the relationship between anemia during pregnancy and small for gestational age (SGA). Therefore, the present systematic review and meta-analysis was conducted to determine the relationship between maternal anemia during pregnancy and SGA.

Method: This meta-analysis was conducted without time limit until April 2017 based on the PRISMA protocol. Several international databases including Cochrane, Scopus, Web of Science (ISI), Pubmed, Embase, and Google Scholar search engine were searched independently by two researchers. The keywords include: anemia, pregnant women, gestational age, and pregnancy. The relative risk (RR) and 95% confidence interval were estimated regarding to the significance of the I² index based on the random effects model. Data were analyzed using Comprehensive Meta-Analysis Software version 2.

Results: Ten studies with a sample size including 620 080 pregnant women entered the meta-analysis process. The overall relationship between maternal anemia during pregnancy and SGA was not significant (RR?=?1.11 [95%CI: 0.99–1.24, p?=?.074]). The relationship between anemia during pregnancy and SGA based on pregnancy trimester showed that maternal anemia was significant in the first trimester, (RR?=?1.11 [95%CI: 1–1.22, p?=?.044]), but this relationship was not significant in the second trimester (RR?=?1.11 [95%CI: 0.85–1.18, p?=?.91]).

Conclusions: Maternal anemia in the first trimester of pregnancy can be considered as a risk factor for negative pregnancy outcomes (SGA).     

小于胎龄儿追赶生长与胰岛素抵抗的研究进展

小于胎龄儿（small for gestational age,SGA）多提示存在胎儿生长受限。追赶生长是纠正生长不利因素后儿童生长发育的补偿机制,因此在大部分SGA中可以观察到追赶生长现象。大量研究认为追赶生长与生命早期发生胰岛素抵抗高度相关,但目前关于追赶生长导致胰岛素抵抗的确切机制缺乏清晰的认识,因而也缺乏针对追...     

Effects of smoking and preeclampsia on birth weight for gestational age

Objective: A counterintuitive interaction between smoking during pregnancy and preeclampsia on birth weight for gestational age (BWGA) outcomes was recently reported. In this report, we examine the relationship between these factors in a well-documented study population with exposure data on trimester of maternal smoking.

Methods: Preeclamptic (n?=?238), gestational hypertensive (n?=?219), and normotensive women (n?=?342) were selected from live-births to nulliparous Iowa women. Disease status was verified by medical chart review, and smoking exposure was assessed by self-report. Fetal growth was assessed as z-score of BWGA. Multiple linear regression was used to test for the association of maternal smoking and preeclampsia with BWGA z-score.

Results: There was no interaction between smoking with preeclampsia or gestational hypertension on fetal growth. BWGA z-scores were significantly lower among women with preeclampsia and those who smoked any time during pregnancy (β?=??0.33, p?=?<0.0001 and β?=??0.25, p?=?0.05) compared to normotensive and non-smoking women, respectively. Infants of women with gestational hypertension were comparable in size to infants born to normotensive women.

Conclusions: Women who developed preeclampsia and those who smoked during pregnancy delivered infants that were significantly smaller than infants of women who did not develop preeclampsia and non-smoking women, respectively.     

Ultrasound estimation of fetal weight in small for gestational age pregnancies

Objective.?Approximately half of small for gestational age (SGA) cases are due to maternal or fetal pathology, and may result in significant neonatal morbidity and mortality. The estimated fetal weight (EFW) measurement is the cornerstone of ultrasonographic findings when diagnosing and managing SGA pregnancies. Our objective was to determine the ultrasound accuracy of EFW in SGA pregnancies.

Methods.?A retrospective chart review was performed of all pregnancies complicated by SGA from a single institution (Stanford University) over a 2-year-period (2004–2006). SGA was defined as EFW?≤?10%. 98 neonates whose last ultrasound for EFW occurred within 7 days of delivery were included in the study. The absolute differences between the EFW and birthweight (BW) were analyzed, and the absolute percent errors were calculated as (EFW???BW)/BW?× 100. The mean absolute differences and mean absolute percent errors were analyzed across all gestational ages (GA) and EFWs using one-way analysis of variance.

Results.?The mean absolute percent error for the entire cohort was 8.7% (±6.3%). There was no statistically significant difference in the mean absolute percent error across all GAs (<32 weeks, 32–36 weeks, >36 weeks), and EFWs (<1500?g, 1500–2000?g, >2000?g).

Conclusion.?Ultrasound measurement of EFW in SGA pregnancies is consistent across all GAs and EFW measurements.     

The utility of ultrasound in late pregnancy compared with clinical evaluation in detecting small and large for gestational age fetuses in low-risk pregnancies

Objective: To determine the utility of ultrasound (US) in late pregnancy for identifying fetuses with growth disturbances.

Methods: This study was designed as a retrospective study of birth weights over a 12-month period at the Royal Hobart Hospital (RHH) and Barwon Health (BH). Data were collected from the discharge summaries and medical records at both hospitals targeting abnormal fetal weight below 10th percentile (small for gestational age – SGA) and above 90th percentile (large for gestational age – LGA).

Results: There were 4079 study patients from both hospitals. After weight adjustment by gender and gestational age, an abnormal fetal weight was detected in 741 cases (babies over the 90th percentile or below 10th percentile). One hundred and twenty-eight patients with high-risk pregnancies were excluded. Therefore, a total of 613 patients remained that were considered to be low-risk pregnancies with abnormal foetal growth; 305 patients from RHH and 308 from BH. The antenatal detection rate for LGA was 35.9%, at RHH by combination of US and clinical evaluation, while for BH it was 34.8% by clinical evaluation alone (p?=?0.910). The antenatal detection rate for SGA was 36.8% via US and clinical evaluation at RHH and 54.5% by clinical evaluation alone at BH (p?=?0.006).

Conclusion: This study shows no benefit in the use of routine US for the antenatal diagnosis of LGA compared with clinical evaluation in low-risk pregnancies. US evaluation was inferior to clinical evaluation in the antenatal diagnosis of SGA in low-risk pregnancies.     

Investigation and management of the small for gestational age fetus

The desire to identify the small for gestational age fetus is due to its association with stillbirth and poorer neonatal outcomes. The difficulty lies in determining which of these babies are just constitutionally small and healthy and which are growth restricted fetuses that are at significant risk of poor outcomes. Fetal growth restriction is often mediated through placental disease and shares a similar aetiological pathway to preeclampsia. Placental malperfusion results in impaired nutrient and oxygen delivery to the fetus. Appropriate risk assessment in early pregnancy and monitoring with symphysis fundal height measurement or ultrasound scans is a crucial part of the screening pathway. There is no effective treatment for growth restriction, so management is based on close monitoring and early delivery. Fetal growth restriction has better defined monitoring and delivery timing guidelines whereas it is more unclear and variable for fetuses considered only to be small for gestational age.     

The effects of maternal obesity on perinatal outcomes among those born small for gestational age*

Background: Maternal obesity has been associated with higher birth weight. Small for gestational age (SGA) neonates born to obese women may be associated with pathological growth with increased neonatal complications.

Methods: This was a retrospective cohort study of all non-anomalous singleton neonates born in Texas from 2006–2011. Analyses were limited to births between 34 and 42 weeks gestation with birth weight?≤10th percentile. Results were stratified by maternal pre-pregnancy BMI class. The risk for stillbirth, neonatal death, neonatal intensive care unit (NICU) admission and five?minute Apgar scores?<7 were estimated for each obesity class and compared to the normal weight group. Multivariable logistic regression analyses were performed to control for potential confounding variables.

Results: The rate of stillbirth was 1.4/1000 births for normal weight women, and 2.9/1000 among obese women (p?0.001, aOR: 1.83 [1.43, 2.34]). The rate of neonatal deaths among normal weight women was 4.3/1000 births, whereas among obese women it was 4.7/1000 (p?=?0.94, aOR: 1.10 [0.92, 1.30]). A dose-dependent relationship between maternal obesity and stillbirths was seen, but not for other neonatal outcomes.

Conclusion: Among SGA neonates, maternal pre-pregnancy obesity was associated with increased risks for stillbirth, NICU admission and low Apgar scores but not neonatal death.     

The association between customised small for gestational age infants and pre-eclampsia or gestational hypertension varies with gestation at delivery

OBJECTIVES: (1) To describe the association between small for gestational age (SGA) infants and pre-eclampsia (PE) and gestational hypertension (GH) and (2) to determine how this association changes with gestational age at delivery using customised centiles to classify infants as SGA. DESIGN: A retrospective observational study. SETTING: National Women's Hospital, a Tertiary Referral Centre in Auckland, New Zealand. POPULATION: A total of 17 855 nulliparous women delivering between 1992 and 1999. METHODS: A comparison of the number of women with a customised SGA infant, PE and GH according to gestational age at delivery. MAIN OUTCOME MEASURES: The incidence of SGA infants (defined as birthweight <10th customised centile), PE and GH at <34, 34-36(+6) and > or =37 weeks. RESULTS: A total of 1847 (10.3%) infants were SGA, 520 (2.9%) women had PE and 1361 (7.6%) had GH. SGA, PE and GH all occurred more commonly with increasing gestation at delivery with 85%, 62% and 90% of cases delivered at term. In women delivering SGA infants, coexisting PE was more likely to occur among those delivered preterm than at term (38.6% at <34 weeks [relative risk, RR 10.2 95%CI 7.3-14.4], 22.4% at 34-36(+6) weeks [RR 6.0 95%CI 4.1-8.6] and 3.8% at > or =37 weeks [OR 1.0]). Women with preterm PE were more likely to have a SGA infant than women with term PE (57.1% at <34 weeks [RR 3.1 95%CI 2.3-4.2], 31.7% at 34-36(+6) weeks [RR 1.7 95%CI 1.2-2.5]) and 18.3% at > or =37 weeks [OR 1.0]). There was a similar association between GH and SGA infants as gestation advanced (57.6% at <34 weeks [RR 4.8 95%CI 3.4-6.6], 30.5% at 34-36(+6) weeks [RR 2.5 95%CI 1.8-3.5] and 12.1% > or =37 weeks [OR 1.0]). CONCLUSIONS: SGA infants and PE are more likely to coexist in preterm births compared with term births. This is likely to reflect the degree of placental involvement in each disease process.     

Outcome of singleton preterm small for gestational age infants born to mothers with pregnancy-induced hypertension. A population-based study

Background: Pregnancy-induced hypertension (PIH) has been associated with a decreased risk of infant mortality in small for gestational age (SGA) preterm infants.

Objective: To evaluate the influence of PIH on mortality and major neonatal morbidities in singleton preterm SGA infants, in the presence and absence of acute pregnancy complications.

Methods: Population-based observational study of singleton SGA infants, born at 24 to 32 weeks gestation in the period 1995–2010 (n?=?2139). Multivariable logistic regression analyses were used to assess the independent effect of PIH on mortality and neonatal morbidities. Acute pregnancy complications comprised premature labor, premature rupture of membranes >6?h, antepartum hemorrhage and clinical chorioamnionitis.

Results: In the absence of pregnancy complications, the odds ratio (95% confidence interval) for mortality (0.77; 0.50–1.16), survival without severe neurological morbidity (1.14; 0.79–1.65) and survival without bronchopulmonary dysplasia (BPD) (0.85; 0.59–1.21) were similar in the PIH versus no-PIH groups. In the presence of pregnancy complications, mortality (0.76; 0.40–1.44), survival without severe neurological morbidity (1.16; 0.64–2.12) and survival without BPD (1.04; 0.58–1.86) were also similar in the PIH versus no-PIH groups.

Conclusions: PIH was not associated with improved outcome in preterm SGA infants, both in the presence and absence of acute pregnancy complications.