Identification of small for gestational age by population-based and customized growth charts in newborns of obese and normal-weight primiparous women

Objective: Our hypothesis was that newborns of obese mothers would be more likely to be classified as small for gestational age (SGA) by their customized growth curves than by the standard growth curves when compared to newborns of normal-weight mothers.

Methods: This is a retrospective cohort of primiparous patients delivering between 1 July 2008 and 30 June 2012. Normal-weight was defined as BMI?≤25?kg/m² and obese as BMI?≥?30?kg/m². Infant birth-weight was characterized as SGA or non-SGA from the Lubchenco curve, the Fenton Preterm Growth Chart, and the customized growth curve.

Results: Infants were more likely to be classified as SGA on the customized curve compared with Lubchenco curve. Odds ratio was 2.8 (CI: 1.7–4.4; p?=?0.001) for obese women and was 2.9 (CI: 1.7–5.1; p?<?0.001) for normal-weight women. Infants were also more likely to be classified as SGA based on the customized curve compared with the Fenton Preterm Growth Curve. The odds ratio was 2.3 (CI: 1.4–3.8; p?=?0.001) for obese women and was 1.5 (CI: 1.01–2.33; p?=?0.04) for normal-weight women.

Conclusions: Population-based curves may mask SGA in obese women. Our study demonstrates that customized growth curves identify more SGA than population-based growth curves in obese and normal-weight women.     

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 influence of fetal sex on the antenatal diagnosis of small for gestational age

Objective: We evaluated the influence of fetal sex on the antenatal diagnosis and detection of small for gestational age (SGA).

Methods: The cohort consisted of unselected singleton pregnancies, undergoing routine biometry and cerebroplacental ratio (CPR) assessment at 36 weeks. Locally fitted equations for centiles and Z scores were used. “Ultrasound SGA” was defined as estimated fetal weight (EFW)?Results: Among 4112 pregnancies, there were 235 female “ultrasound SGA” fetuses and 177 male; (odds ratios (OR) 1.502 (1.223???1.845)); the detection rate of SGA at birth was 50.6% and 40.9%, respectively (OR 1.479 (0.980???2.228)). In “ultrasound SGA” girls the abdominal circumference growth velocity (ACGV) between 20 and 36 weeks was less frequently in the lowest decile (OR 0.490 (0.320???0.750)), with no differences in CPR.

Conclusions: Females are more commonly diagnosed as SGA; those diagnosed may be at less risk than males.     

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.     

Low maternal awareness of fetal movement is associated with small for gestational age infants

Our aim was to identify associations between information given to pregnant women about fetal activity, level of maternal awareness of fetal activity, maternal concern about decreased fetal movement, and pregnancy outcomes. This was a population-based cross-sectional study. Mothers with a singleton delivery were invited to answer an anonymous structured questionnaire before discharge from the delivery unit. Six hundred and ninety-one mothers participated (60.4% of eligible women). Women were highly aware of fetal activity. Yet, 25% did not receive any information from care providers about expected normal fetal activity. Receiving information about fetal activity was associated with increased maternal awareness (odds ratio, 2.0; 95% confidence interval [CI], 1.2-3.4). Low maternal awareness of fetal activity was associated with an increased risk of having a small for gestational age infant (odds ratio, 6.5; 95% CI, 3.5-12.3). Expectations about the normal frequency of fetal movements, as reported by the mothers, varied from 25 kicks/hour to 3 kicks/24 hours. Receiving information about expected fetal activity was associated with maternal concerns about decreased fetal movement, but not with improved outcomes. We conclude that receiving information about expected fetal activity was associated with maternal concerns, but not with improved outcomes.     

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.     

Prediction of small for gestational age by logistic regression in twins

BACKGROUND: Small for gestational age (SGA) is one of the major determinants of perinatal mortality and morbidity, and may relate in adult diseases. Early prediction of SGA could be helpful for health care providers and public health workers in guiding antenatal management and prevention. The reported methods of SGA prediction are not satisfactory because the diagnostic performance is poor and the interval between prediction and delivery is too short. AIMS: To establish a SGA prediction model for twin pregnancies based on variables obtainable in early gestation. METHODS: We used a large twin registry United States data (1995-1997). The study subjects were randomly divided into two groups: group 1 to establish the prediction model by logistic regression and group 2 to validate the prediction model. SGA was defined as birth weight for gestational age z scores less than 10th percentiles. Pair of twin was the unit of analysis. Two sets of multiple logistic regression analyses with different outcome measures - one or both twins SGAs and both twins SGAs - were used to establish the prediction model. RESULTS: The sensitivity, specificity, and positive predictive value were 52.3, 62.5, and 21.5%, respectively, at the cutoff value 0.16 in a SGA prediction model based on maternal race, education, marital status, parity, prenatal care visit initiation, cigarette smoking, and paternal race. CONCLUSIONS: A prediction model based on determinants that can be obtained at early gestation might be useful in the management of pregnancies with high risk of SGA in twins.     

A comparison of customized and population-based birth-weight standards: The influence of gestational age

Objectives

We examined how customized birth-weight standards compare to population birth-weight references at term (≥37 weeks), nearly term (34–36 weeks), moderately preterm (32–33 weeks) and for the very preterm births (28–31 weeks), with respect to perinatal mortality.

Study design

Data from the national Swedish Medical Births Register for the years 1992–2001, consisting of a total of 783,303 singletons born at or after 28 completed gestational weeks. Infants were classified as small for gestational age (SGA, <10th centile) according to a conventional population based birth-weight reference and a customized standard. Risk ratios (RR) for still birth and neonatal death were compared between standards by prematurity of the birth. Diagnostic performance measures of specificity, sensitivity and positive and negative predictive values were also evaluated.

Results

More than half, 59% (209), of the 355 infants still-born between 28 and 31 weeks gestation were classified as SGA by the customized standard, but only 23% (80), were so classified as SGA by the population reference. However, only 14% (95%CI 13–16) of the 1461 very preterm infants classified as SGA by the customized standard were still-born, compared to 23% (95%CI 19–28) of the 348 infants classified as SGA by the population reference. Therefore, the relative risk of still birth for those classified as SGA by the customized standard is lower, 2.02 (95%CI: 1.65, 2.46), than for the population reference 2.64 (95%CI: 2.11, 3.30). Similar results were observed for the risk of neonatal death. For term weeks, customized standards showed stronger relationships than population references (RR: 4.30 (95%CI 3.82, 4.84) vs. 4.00 (95%CI 3.55, 4.51) for still births).

Conclusions

Customized standards categorize a higher absolute number of preterm infants who are still-born as SGA. However, infants classified as SGA by population references are at higher risk of perinatal mortality than infants classified as SGA by customized standards.     

Endocrine regulation in asymmetric intrauterine fetal growth retardation

Objective. The ponderal index (PI) is a widely accepted measure of disproportionate growth or asymmetrical growth retardation by pediatricians worldwide. Identification of disproportionately grown small for gestational age (SGA) neonates by using the ponderal index as a measure of the nutritional status at birth, is important because they constitute a high-risk group among SGA neonates. Poor nutritional status of the mother could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in an increased incidence of intrauterine growth-retarded (IUGR)/SGA births. IUGR is a significant risk factor for adult disease. In this study, we have investigated the endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor nutritional status of the mother.

Materials and methods. We examined the quantitative variations in hormonal and growth factor profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on their growth status into SGA and appropriate for gestational age (AGA).

Results. (1) A total of 24.7% neonates had a PI < 2, indicating a high incidence of asymmetric IUGR in the population studied. (2) Anthropometric parameters measured in the mothers indicate that the mothers giving birth to neonates with a PI < 2 had poor nutritional status, both prior to and during pregnancy. (3) We observed increased levels of placental lactogen and prolactin and decreased levels of insulin in the cord blood of neonates with PI < 2, while lower levels of insulin-like growth factor 1 (IGF-1) and higher levels of epidermal growth factor (EGF) were observed in their mothers.

Conclusion. Poor maternal nutritional status results in fetal adaptation to a growth restricted environment via the modulation of the pituitary–thyroid axis thereby altering the endocrine milieu, thus affecting fetal growth.     

Defining fetal growth restriction: abdominal circumference as an alternative criterion

Purpose: The purpose of this study is to determine if using abdominal circumference percentile (AC) to define fetal growth restriction (FGR) improves ultrasound at ≥36 weeks as a screening test for small for gestational age (SGA).

Materials and methods: All non-anomalous singletons undergoing ultrasound at a single center at ≥36 weeks during 12/2008–5/2014 were included. FGR was defined as (estimated fetal weight) estimated fetal weight (EFW) and/or abdominal circumference (AC)?Results: There were 1594 ultrasounds. Median (IQR) ultrasound GA was 37.3 (36.6–38.0), days to delivery 10.6 (5.0–18.4), and delivery GA 39.29 (38.6–39.9). EFW <10 had the following characteristics: sensitivity 50.6%, FPR 2.0%, PPV 83.8%, and AUC 0.743. Using AC <10, these were 64.0, 2.9, 81.3, and 0.806, respectively. Using AC or EFW <10, these were 67.5, 3.3, 80.3, and 0.821, respectively; this criterion has the largest AUC (p?Conclusions: AC <10 is more sensitive and has a similar PPV compared with EFW <10 for SGA. Using AC <10 or EFW <10 has the best balance of sensitivity and specificity as a screening test and has a low FPR. AC may be a reasonable alternative criterion to EFW for FGR diagnosis.     

Identifying risk factors for premature rupture of membranes in small for gestational age neonates: a population-based study

Objective. To determine the prevalence and risk factors for premature rupture of membranes (PROM) among pregnancies complicated with small for gestational age (SGA) neonates.

Methods. A computerised database was used to identify deliveries of SGA neonates in pregnancies complicated with PROM between the years 1988 and 2002. Pregnancies with PROM and SGA neonates were compared to those with SGA and without PROM. Demographic, obstetric, clinical and labour characteristics were evaluated. Multiple logistic regression analysis was used to determine independent risk factors for PROM in pregnancies complicated by SGA. Statistical analysis was performed with SPSS package.

Results. There were 120 982 deliveries included out of which 6074 (5.99%) presented with appropriate for gestational age (AGA) neonates and PROM. A total of 1077 delivered SGA infants complicated with PROM (5.5%). After adjustment for confounding variables, the following characteristics were significantly associated with PROM and SGA: Jewish ethnicity, parity and cervical incompetence. The following complications were associated with PROM and SGA: arrest of labour, fetal distress, failed induction, cesarean delivery, clinical chorioamnionitis and placenta accreta. No significant differences regarding low Apgar scores and perinatal mortality rates were noted.

Conclusions. The risk of PROM among patients with SGA is lower than in AGA infants. Parity and cervical incompetence are risk factors for PROM among women who delivered SGA neonates. In this population there is a higher rate of arrest of labour, chorioamnionitis, fetal distress and cesarean delivery. Neonatal outcome and perinatal mortality are similar in both groups.     

The customized fetal growth potential: a standard for Ireland

Objective

To identify maternal and pregnancy-related physiological and pathological variables associated with fetal growth and birthweight in Ireland and to develop customized birthweight centile charts for the Irish population that will aid in appropriate identification and selection of growth-restricted fetuses requiring increased antenatal surveillance.

Study design

Prospectively collected outcome data of 11,973 consecutive ultrasound-dated singleton pregnancies between 2008 and 2009 from six maternity units in Ireland (Dublin, Galway, Limerick and Belfast) were included for analysis. Maternal weight and height at booking, parity and ethnicity were recorded and combined with birthweight, fetal gender and pregnancy outcomes. Coefficients were derived by backward multiple regression using a stepwise backward elimination approach.

Results

A total of 11,973 ultrasound-dated singleton pregnancies were included in the analysis. Over 90% of women (n = 10,850) were of Irish or European descent, 3.4% (n = 407) were African or African Caribbean, 1.7% (n = 208) were Indian; 42.2% (n = 5057) were nulliparous, 32.8% (n = 3923) had one previous delivery after 24 weeks’ gestation, 15.6% (n = 1872) had two previous deliveries and 9.4% (n = 1121) had three or more previous deliveries. Mean term birthweight for a standard Irish mother was 3491grams. Babies of all other ethnic origins were smaller than their Irish counterparts. African Caribbean, Bangladeshi, Indian and Pakistani babies were on average 237 g, 196 g, 181 g and 181 g lighter, respectively, when compared to the average Irish offspring. Pathological factors significantly affecting term birthweight were pre-gestational diabetes (+137 g; p < 0.001), smoking (−225 g; p < 0.001), pregnancy-induced hypertension (−37.6 g; p = 0.009) and maternal obesity (−41.6 g; p = 0.012).

Conclusion

Birthweight in this Irish maternity population is subject to similar influences to those observed in studies from the UK, Sweden, USA and Australasia. The derived coefficients can be used for customized assessment of fetal growth potential in Ireland. The implementation of these customized centile charts and their free online availability will aid clinicians in Ireland in the interpretation of fetal weight estimation.     

Pregnancy outcome and placental pathology in small for gestational age neonates in relation to the severity of their growth restriction

Purpose: To investigate neonatal outcome and placental pathology in pregnancies complicated with small for gestational age neonates (SGA), in relation to the severity of growth restriction.

Methods: The medical records and placental histology reports of all neonates with a birth-weight (BW) ≤10th percentile, born between 24–42 weeks, during 2010–2015, were reviewed. Placental lesions were classified into maternal and fetal vascular malperfusion (MVM and FVM) lesions. Results were compared between neonates with BW <5th percentile (severe SGA group), neonates with BW between 5th–10th percentile (mild SGA group) and a control group of appropriate for gestational age (AGA) neonates. Composite neonatal outcome was defined as one or more of early complications.

Results: Overall, 753 neonates were included, 238 in the severe SGA group, 266 in the mild SGA group, and 249 in the control group. The severe SGA group had higher rates of composite adverse neonatal outcome as compared with the mild SGA and control groups (37.2 versus 17.6%, versus 24.5%, respectively, p?p?Conclusions: Worse neonatal outcome and more placental MVM and FVM lesions correlate with the severity of neonatal growth restriction in a “dose-dependent” manner.     

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.     

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).     

Placental gene expression of transforming growth factor beta 1 (TGF-β1) in small for gestational age newborns

Objective: The gene expression of transforming growth factor beta-1 (TGF-β1) in human placental samples obtained from pregnancies with small for gestational age fetuses (SGA) was compared to those of normal pregnancies.

Methods: In 2011 placental samples from 101 pregnancies with SGA and from 140 normal pregnancies were obtained for analysis of TGF-β1 gene expression. Several clinical parameters were also assessed for correlation between genetic and clinical parameters.

Results: There were no significant differences in gene activity of the TGF-β1 gene between the SGA versus normal pregnancy groups (Ln2^α: 0.16; p?=?0.07). Within the SGA group, no fetal gender-dependent differences were seen in TGF-β1 gene expression (Ln2^α: ?0.11; p?=?0.05). Similarly, no significant differences in gene activity were observed by the degree of severity of SGA as assessed by percentile fetal birth-weight (Ln2^α: 0.32; p?=?0.06).

Conclusion: We found no change in gene expression of TGF-β1 in placental samples obtained from SGA pregnancies versus normal pregnancy suggesting an absence of a direct role of the TGF-β1 gene in the development of SGA. However, the absence of increased gene expression of TGF-β1 in SGA can be conceptualized as a failure to mount a compensatory response in the SGA environment.     

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...