The use of customised versus population-based birthweight standards in predicting perinatal mortality

OBJECTIVE: The objective of this study was to critically examine potential artifacts and biases underlying the use of 'customised' standards of birthweight for gestational age (GA). DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: A total of 782,303 singletons > or =28 weeks of gestation born in 1992-2001 to Nordic mothers with complete data on birthweight; GA; and maternal age, parity, height, and pre-pregnancy weight. METHODS: We compared perinatal mortality in four groups of infants based on the following classification of small for gestational age (SGA): non-SGA based on either population-based or customised standards (the reference group), SGA based on the population-based standard only, SGA based on the customised standard only, and SGA according to both standards. We used graphical methods to compare GA-specific birthweight cutoffs for SGA using the two standards and also used logistic regression to control for differences in GA and maternal pre-pregnancy body mass index (BMI) in the four groups. MAIN OUTCOME MEASURES: Perinatal mortality, including stillbirth and neonatal death. RESULTS: Customisation led to a large artifactual increase in the proportion of SGA infants born preterm. Adjustment for differences in GA and maternal BMI markedly reduced the excess risk among infants classified as SGA by customised standards only. CONCLUSION: The large increase in perinatal mortality risk among infants classified as SGA based on customised standards is largely an artifact due to inclusion of more preterm births.     

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.     

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.     

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.     

Uterine and umbilical artery Doppler are comparable in predicting perinatal outcome of growth-restricted fetuses

Objective  To compare umbilical and uterine artery Doppler in predicting outcome of pregnancies suspected of fetal growth restriction (FGR).
Design  A prospective study included 353 singleton pregnancies complicated by an FGR fetus.
Setting  University Hospital setting.
Sample  Pregnancies suspected of FGR diagnosed by ultrasound fetal biometry during a 5-year period.
Main outcome measure  Perinatal outcome in relation to uterine and umbilical artery Doppler.
Methods  The women underwent Doppler examination of the umbilical and uterine arteries. Results from the uterine, but not the umbilical artery, were blind to the woman and managing obstetrician. The Doppler results were related to perinatal outcomes including small for gestational age newborns, caesarean delivery, premature delivery (<37 weeks of gestation) and admission of the newborn to a neonatal intensive care unit.
Results  Abnormal uterine artery Doppler velocimetry was seen in 120 (33.4%) pregnancies and abnormal umbilical artery Doppler in 102 (28.4%). There was a statistically significant correlation between abnormal Doppler of both the umbilical and uterine arteries and adverse outcome of pregnancy. The two vessels were comparable in predicting adverse outcome. Women with normal umbilical artery Doppler (251) were analysed separately. Abnormal uterine artery Doppler, seen in 61 (24.3%) of those women, showed a statistically significant correlation for adverse outcome of pregnancy.
Conclusions  Doppler examinations of the uterine and/or the umbilical arteries seem to be comparable as predictors of outcome in pregnancies complicated by FGR. Including uterine artery Doppler in the surveillance of growth-restricted fetuses might detect a group of pregnancies at high risk, even though the umbilical artery Doppler was normal.     

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.     

Customized weight curves for Spanish fetuses and newborns

Abstract

Objectives: To construct a model of customized birthweight curves for use in a Spanish population.

Materials and methods: Data of 20 331 newborns were used to construct a customized birthweight model. Multiple regression analysis was performed with newborn weight as the dependent variable and gestational age (GA), sex and maternal (M) weight, height, parity and ethnic origin as the independent variables. Using the new model, 27?507 newborns were classified as adequate for GA (AGA), large for GA (LGA) or small for GA (SGA). The results were compared with those of other customized and non-customized models.

Results: The resulting formula for the calculation of optimal neonatal weight was:

Optimum weight (g)?=?3289.681?+?135.413*GA40–14.063*GA40²–0.838*GA40^3?+?113.889 (if multiparous)?+?165.560 (if origin?=?Asia)?+?161.550 (South America)?+?67.927 (rest of Europe)?+109.265 (North Africa)?+?9.392*Maternal-Height?+?4.856*Maternal-Weight–0.098*Maternal-Weight^2?+?0.001*Maternal-Weight^3?+?67.188*Sex?+?GA40*(6.890*Sex?+?9.032 (If multiparous)?+0.006*Maternal-Height^3?+?0.260*Maternal-Weight)?+?GA40² (?0.378*Maternal-Height – 0.008*Maternal-Height²)?+?GA40³ (?0.032*Maternal-Height).

Weight percentiles were obtained from standard data using optimum weight variation coefficient. Agreement between our customized model and other Spanish models was “good” (κ?=?0.717 and κ?=?0.736; p?<?0.001).

Conclusions: Our model is comparable to other Spanish models, but offers the advantage of being customized, updated and freely available on the web. The 30.6% of infants classified as SGA using our model would be considered as AGA following a non-customized model.     

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.     

Use of uterine Doppler in an Australian level II maternity hospital

OBJECTIVE: To evaluate the clinical usefulness of uterine Doppler. DESIGN: Retrospective study between March 2001 and March 2003. SETTING: A high-risk population of pregnant women in a busy level II Maternity unit. METHODS: Resistance index (RI) measurements of the right and left uterine artery were obtained by using pulsed wave Colour Doppler. The presence of a unilateral or bilateral early diastolic notch was noted. An abnormal result was defined as a mean RI >or= 0.58 with no, one or two notches or a mean RI < 0.58 in the presence of bilateral notches. RESULTS: Pre-eclampsia was found in 45 (24.7%) women, gestational hypertension (GH) in 22 (12.1%) and intrauterine growth restriction (IUGR) in 42 (23.1%) of women included (total 59.9%). In the overall group, 127 (69.8%) women were found to have abnormal uterine artery Doppler results and 55 (30.2%) of patients had a normal Doppler study. No significant differences were found between the group of women with abnormal uterine artery Doppler and the women with a normal velocity waveform in the prediction of pre-eclampsia, IUGR and GH, this was also true in the various high-risk-subgroups. CONCLUSIONS: Uterine Doppler is not particularly useful to the obstetrician in the management of patients with an a priori very high risk to develop uteroplacental insufficiency.     

The value of customised centiles in assessing perinatal mortality risk associated with parity and maternal size

Objective  We wanted to compare customised and population standards for defining smallness for gestational age (SGA) in the assessment of perinatal mortality risk associated with parity and maternal size.
Design  Population-based cohort study.
Setting  Sweden.
Population  Swedish Birth Registry database 1992–1995 with 354 205 complete records.
Method  Coefficients were derived and applied to determine SGA by the fully customised method, or by adjustment for fetal sex only, and using the same fetal weight standard.
Main outcome measure  Perinatal deaths and rates of small for gestational age (SGA) babies within subgroups stratified by parity, body mass index (BMI) and maternal size within the BMI range of 20.0–24.9.
Results  Perinatal mortality rates (PMR) had a U-shaped distribution in parity groups, increased proportionately with maternal BMI, and had no association with maternal size within the normal BMI range. For each of these subgroups, SGA rates determined by the customised method showed strong association with the PMR. In contrast, SGA based on uncustomised, population-based centiles had poor correlation with perinatal mortality. The increased perinatal mortality risk in pregnancies of obese mothers was associated with an increased risk of SGA using customised centiles, and a decreased risk of SGA using population-based centiles.
Conclusion  The use of customised centiles to determine SGA improves the identification of pregnancies which are at increased risk of perinatal death.     

Fetal growth restriction and other risk factors for stillbirth in a New Zealand setting

BACKGROUND: Stillbirth affects almost 1% of pregnant women in the Western world but is still not a research priority. AIMS: To assess in a cohort of stillbirths: the demographic risk factors, the prevalence of small for gestational age (SGA) by customised and population centiles, and the classification of death using the Perinatal Society of Australia and New Zealand Perinatal Death Classification (PSANZ-PDC). METHODS: The study population comprised 437 stillborn babies (born from 1993 to 2000 at National Women's Hospital, Auckland, New Zealand) and their mothers. The referent population for demographic factors was live births n=69 173. RESULTS: After multivariable analysis, risk factors for stillbirths were: Indian (odds ratio (OR) 1.85, 95%CI (1.18, 2.91)), or Pacific Islander (OR 1.65, 95%CI (1.27, 2.14)); smoking (OR 1.33, 95%CI (0.99, 1.79)) or unknown smoking status (OR 2.87, 95%CI (2.30, 3.58)); nulliparity (OR 1.42, 95%CI (1.10, 1.83)), and para 2 (OR 1.36, 95%CI (1.01, 1.83)). One hundred and twenty-nine (46%) stillbirths born>or=24 weeks (n=278) were SGA by customised, and 94 (34%) by population centiles. Customised SGA was more common in preterm versus term stillbirths (101 of 198 (51%) vs 28 of 80 (35%), respectively, P=0.02) but rates of population SGA did not differ (72 of 198 (36%) vs 22 of 80 (28%) P=0.16). 'Spontaneous preterm' was the most common cause of stillbirth at <28 weeks and 'unexplained' at >or=28 weeks using PSANZ-PDC classification. CONCLUSIONS: This study again emphasises the importance of suboptimal fetal growth as an important risk factor for stillbirth. Customised centiles identified more stillborn babies as SGA than population centiles especially preterm.     

Building consensus and standards in fetal growth restriction studies

Fetal growth restriction is a pathologic condition in which the fetus fails to reach its biologically based growth potential. There is inconsistency in terminology, definition, monitoring, and management, both in clinical practice and in the existing literature. This hampers interpretation and comparison of cohorts and studies. Standardization is essential.With the lack of a golden standard, or the opportunity to come to empirical evidence, consensus procedures can help to establish standardization. Consensus procedures provide no new information but formulate an agreement (as second best in the absence of robust evidence) for clinical and/or research practice on the basis of existing data. Consensus agreements need to be updated when new evidence becomes available and can change over time.In this chapter, we address the different issues that lack uniformity in FGR studies and management. Furthermore, we discuss several consensus methods and recent consensus procedures regarding fetal growth restriction.     

Early neonatal hypoglycemia: incidence of and risk factors. A cohort study using universal point of care screening

Objective: The objective of this study is to determine the true incidence of early neonatal hypoglycemia and to confirm potential risk factors.

Study design: The study was conducted at tertiary Medical Center in Israel, between June and September 2014. First blood glucose concentrations of all infants admitted to the nursery were measured using a “point of care” analyzer (Accu-Chek). We recorded risk factors for hypoglycemia such as birth weight, gestational age, maternal diabetes and demographics and analyzed their association with two hypoglycemia cutoffs: 40 and 47?mg/dl.

Results: Of 4000 newborns admitted during that period, 3595 were analyzed after excluding 405 who had missing data. Glucose level was obtained at a mean age of 74?±?30?min. One hundred and twenty-four newborns (3.4%) had blood glucose levels below 40?mg/dl and 435 (12.1%) below 47?mg/dl. Univariate analyses revealed that gestational age, maternal diabetes, low birth weight (<2500?g), and twin delivery were associated with early neonatal hypoglycemia. Other risk factors (e.g. large or small for gestational age, birth weight >3800?g) were not. In multivariate analysis, gestational age remained the strongest association, while maternal diabetes and low birth weight became non-significant.

Conclusions: We showed a high occurrence of early hypoglycemia in normal newborns using universal screening. The strongest risk factor was early gestational age. Surprisingly, incidence of early hypoglycemia in the presence of other classical risk factors was like that of the general population.