Usefulness perinatal prognosis assessment using z-score over current low birth weight metric: a descriptive study

doi:10.21203/rs.3.rs-5269171/v1

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Usefulness perinatal prognosis assessment using z-score over current low birth weight metric: a descriptive study

https://doi.org/10.21203/rs.3.rs-5269171/v1

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Background: A cut-off weight of 2500 g in infants, which is commonly referred as low birth weight infants, was established as an indicator of perinatal prognosis several decades ago.

However, perinatal medicine developed dramatically since then and theoutcomes are discussed using other factors including fetal growth nowadays.

This study was conducted to assess the present perinatal situation with recent assessment scales and reconsider the indicators used for perinatal outcome.

Methods: This is a retrospective descriptive study analyzing whole Japanese birth certificate data between 1992 and 2018. Trend in prenatal outcomes including birth weight, gestational age, presence of fetal growth restriction, preterm birth and birth weight-to-gestational age z-score were calculated. Fetal growth restriction was defined as birth weight-to-gestational age z-score less than 10 percentile.

Results: A total of 48,235,783 births in Japan were included. The proportion of infants with birth weight under 2500 g was constant while mean birth weight stopped declining and mean gestational age continued to fall. In contrast, the incidence of fetal growth restriction and the mean birth weight-to-gestational age z-score were improving. In detail, proportion of early term infants (between 37 weeks 0 day and 38 weeks 6 days of gestational age) was increasing while that of late preterm infants (between 34 weeks 0 day and 37 weeks 6 days of gestational age) was constant.

Conclusions: Over all perinatal outcome was improving. Shortened gestational age result from change in perinatal management policy due to progress in perinatal medicine that enabled smaller infants and/or infants born at shorter gestational age to survive. However, even if delivered with a shorter gestational period with an aim to achieve good outcomes, considering that the 10th percentile weight of a baby boy born to a primiparous mother at 37 weeks 0 days gestation, a full-term delivery, is 2203 g, for example, the infants would be classified as a low birthweight infant which is an indicator for poor prognosis. Therefore, low birth weight no longer reflects perinatal outcome appropriately and other factors like fetal growth should be considered as indicators for overall perinatal context.

Low birth weight (LBW) infants are defined as infants born under 2 500 g, which is a common criterion for prognosis of adverse perinatal outcomes.¹ This cut-off weight of 2 500 g was first proposed in 1919 based on infant outcomes at the time and has been used for infant prognosis since it was established as a criterion for prematurity in the 1930s.² In Japan, the Ministry of Health, Labour, and Welfare (MHLW) reported a prevalence of approximately 9% for LBW in recent years, and identified a need to review the Japanese guidelines for obstetrical practice.³ Nevertheless, perinatal health outcomes have been dramatically improving during this same period, and the incidence of mortality in infants born around 2500 g is no longer high.^4,5 Because of these improvements, it is possible that this single metric, LBW, that was developed nearly a century ago, is no longer suitable for measuring or predicting perinatal performance in modern clinical practice.

LBW is a consequence of fetal growth retardation (FGR) and/or preterm birth (PB), two factors have distinct etiologies; however, when the cut-off criteria of 2 500 g was established, this difference in etiologies was not yet well understood. In these era when neonatal death was mostly attributed to LBW, studies mainly focused on the relationship between birth weight and both short- and long-term outcomes. The most popular study regarding long-term outcomes is the Barker hypothesis,⁶ which proposed an association between LBW and ischemic heart disease. Subsequent research adopted a broader conception of the developmental origins of health and disease (DOHaD) in which the indicator for adverse long-term outcomes shifted from LBW to poor intrauterine and extrauterine environment.⁷ Poor intrauterine environment causes FGR, which complicates a range of prenatal outcomes including perinatal asphyxia, respiratory disease, and renal dysfunction, during the acute phase.⁸ The DOHaD concept suggests that even infants with FGR who survived their perinatal period will still have complications, including poor long-term health outcomes. Our previous study also reported that FGR and shorter gestational age were independent risk factors for poor perinatal outcomes,⁹ and another recent study also reported that these factors should be discussed separately, too. ² This means that understanding FGR independently from other risk factors is important when assessing short- and long-term perinatal outcomes and suggests that LBW is no longer a sufficient or necessary condition for assessing perinatal risks. Therefore, in this study, we aimed to assess the trends in the Japanese perinatal situation using the FGR index in a whole national database.

To understand trend in births, Japanese national birth certificates issued between 1992 and 2018 were obtained from the MHLW for this observational study. Using whole national data, information on birth weight (BW), sex, gestational age (GA), parity, and maternal age were extracted. Birth weight-for-gestational age (BW-for-GA) z-scores were calculated using BW, sex, GA, and parity data using the lambda-mu-sigma method.¹⁰ Race and/or ethnicity were not considered in this study because Japan is a racially homogeneous nation. Infants with BW lower than the 10% percentile were defined as having FGR. PB was defined as < 37 weeks of GA. Additionally, we analyzed the time trend of late and early term births which were defined as birth between 34 weeks 0 days of GA and 36 weeks 6 days of GA, and between 37 weeks 0 days of GA and 38 weeks 6 days of GA, respectively. During 1992–1994, since only gestational week was reported and no gestational day, it was imputed by value of 3. Local polynomial regression was used to estimate the smoothed trend in all outcomes, with optimal span determined using the Bayesian information criterion.

This study was approved by the Ethic Committee of Tokyo Metropolitan Toshima Hospital (Approval number: Rin-jin 6–36).

During the study period, a total of 48 235 783 births were included in this study using birth certificate data obtained from the MHLW. Sample characteristics are shown in Table 1. The total number of births peaked in 1994 and gradually decreased to 918 238 in 2018. The proportion of girls was consistent at 0·49 throughout the study period. The proportion of primiparous mothers was between 0·46 and 0·50. Maternal age increased consistently from 28·42 to 31·48 years during the study period. The mean BW was lowest in 2010 at 3000·27 g but has consistently increased since then. The mean GA was 39·37 in the initial phase of the study and shortened to 39·12 weeks at the end of the study period. Figure 1 shows the trend in the mean BW and GA. We observed a continuous decrease in the mean GA, while the mean BW has not noticeably changed since 2005. Figure 2 shows the trend in the mean BW-for-GA z-score calculated using lambda-mu-sigma method¹⁰ and prevalence of LBW, PB, and FGR. The proportion of infants with LBW and PB has not changed noticeably since 2005, while the proportion with FGR is decreasing and the mean BW-for-GA z-scores is increasing. Figure 3 illustrates the prevalence of PB in more detail and shows the proportion of early term infants (born between 37 weeks 0 day of GA and 38 weeks 6 days of GA) and late-preterm infants (born between 34 weeks 0 day of GA and 37 weeks 6 days of GA). The proportion of early term births is increasing, while there was no increased trend in the late-preterm births.

Table 1

Trend in the characteristics of infants in the data.
Year	Total number of births	Sex (proportion of girl)	Parity (proportion of 0 parity)	Maternal age	Mean BW	Mean Gestational age
1992	1209157	0.49	0.46	28.42	3097.16	NA
1993	1188540	0.49	0.47	28.46	3092.90	NA
1994	1238517	0.49	0.48	28.52	3079.94	NA
1995	1187159	0.49	0.48	28.59	3067.38	39.37
1996	1206784	0.49	0.48	28.69	3066.12	39.35
1997	1191859	0.49	0.48	28.77	3056.68	39.39
1998	1203362	0.49	0.48	28.86	3047.96	39.38
1999	1177841	0.49	0.49	28.93	3038.19	39.36
2000	1190838	0.49	0.49	29.06	3032.56	39.32
2001	1171022	0.49	0.49	29.15	3026.69	39.33
2002	1154205	0.49	0.50	29.29	3021.98	39.33
2003	1123940	0.49	0.49	29.50	3020.05	39.31
2004	1110981	0.49	0.48	29.69	3011.67	39.26
2005	1062725	0.49	0.48	29.87	3007.71	39.26
2006	1092999	0.49	0.48	30.04	3006.21	39.24
2007	1089988	0.49	0.48	30.24	3004.50	39.23
2008	1091316	0.49	0.47	30.37	3003.65	39.20
2009	1070205	0.49	0.48	30.53	3001.98	39.21
2010	1071450	0.49	0.48	30.69	3000.27	39.19
2011	1050950	0.49	0.47	30.81	3002.40	39.18
2012	1037378	0.49	0.47	30.99	3000.73	39.16
2013	1030048	0.49	0.47	31.14	3001.16	39.16
2014	1003824	0.49	0.47	31.25	3001.85	39.16
2015	1005988	0.49	0.48	31.35	3001.42	39.16
2016	977601	0.49	0.47	31.42	3003.96	39.14
2017	946302	0.49	0.46	31.46	3004.51	39.12
2018	918238	0.49	0.46	31.48	3004.91	39.12
The total number of births, sex (female proportion), parity (proportion of primiparous mother), mean maternal age, and mean birth weight are shown.

The present study, which included 48 235 783 infants from Japanese national data, showed a decreased mean GA; meanwhile the mean BW, proportion of FGR, and mean BW-for-GA z-score improved, and the proportion with LBW did not change. The increase in prevalence of early term birth seems to contribute to the decrease in the mean GA. This suggests that while LBW as a prognostic indicator has not improved over this period, all other measures of perinatal risk particularly BW-for-GA z-scorehave improved along with perinatal outcomes, indicating that LBW is of decreasing value as a prognostic indicator.

The decrease in GA likely reflects changes in obstetric management policies. First, a large study reported that planned cesarean section (CS) contributes to better outcomes in breech presentation,¹¹ a finding supported by the committee opinion from The American college of Obstetricians and Gynecologists.¹² Following the Guideline for Obstetrical Practice in Japan, most breech deliveries have also shifted to CS in Japan.¹³ Although our data did not include information about the delivery method, the American College of Obstetricians and Gynecologists reported that the number of practitioners with skills and experience in performing vaginal breech delivery has decreased, and the number of CS has been increasing,¹⁴ which is the same as in Japan.¹³ Therefore, it is likely that a decreasing proportion of the births studied in this research were breech births. Second, the Guideline for Obstetrical Practice in Japan strictly indicated for trial of labor after CS (TOLAC). According to the guideline, obstetric teams must ensure that the following conditions are met when performing TOLAC: emergency CS and emergency surgery for uterine rupture are available; the number of previous CS is one; the previous CS was a transverse submandibular incision; the patient had a good postoperative course; and there was no history of surgery that involved the myometrium or rupture of the uterus. These two policy statements increased the number of elective CS in Japan. Moreover, our data showed increases in the mother’s age which contributed to the increase in the number of mothers with a history of uterine surgery. Increasing age at delivery also contributed to the increasing number of elective CS. Together, these changes likely led to an increased number of elective CS. Notably, MHLW data shows an increase in the percentage of CS from 5% in 1985 to 24·8% in 2014.

There are two options for when to have elective CS: between 39 weeks and 40 weeks of GA, and at 38 weeks of GA. Compared to the first option, the second option had fewer urgent and out-of-hours CS.^15–17 In the present situation in Japan, the second option is preferred because many deliveries are performed in small institutions not adequately prepared for emergency or after-hours CS. Thus, it is likely that the increase in the number of elective CS and earlier timing of CS contributed to the shortening of GA. These policy changes have been made in a bid to improve perinatal outcomes and neonatal care, and have enabled smaller infants to survive.

Another factor that contributed to the shortening of GA is a 2014 change in the Guideline for Obstetrical Practice in Japan, which recommends either inducing or waiting for onset of labor in mothers at 41 weeks of GA, but inducing labor in mothers at 42 weeks of GA,¹⁸ which likely reduced the extrema of GA.

However, elective CSs at earlier GA have several issues.¹⁹ Late-preterm births, defined as delivery between 34 weeks 0 day and 36 weeks 6 days of GA, have higher neonatal mortality and morbidity than term births.²⁰ This is because infants born as late-preterm infants are not fully mature.²¹ Early term infants, defined as infants born between 37 weeks 0 days and 38 weeks 6 days of GA, are more mature than late-preterm infants, but still have higher risk of respiratory management, intravenous fluid treatment, and other complications.²² Our study found no significant change in the proportion of whole PB and early term birth, except for an increase in the proportion of early term deliveries. Therefore, an increased number of elective CSs likely contributed to the increase in the proportion of early term deliveries. Although complications are more likely to occur in infants born at late-preterm than term births,^22,23 developments in Japanese neonatal management have likely led to greater rates of elective CS during the early term period.

Although the current perinatal management policies have been revised several times for better perinatal outcomes, these evaluations have been based on LBW as a prognostic indicator. However, the ten-percentile weight of boys born at 37 weeks 0 days of GA to primiparous mothers is 2203 g, (2282 g in multiparous mothers) while in girls these birthweights are 2115g and 2192 g, respectively. Infants born with an appropriate BW-for-GA have a high likelihood of being labeled as LBW infants under present management policies, increasing the nominal number of LBW infants even though they are unlikely to have significant increased risk of negative perinatal outcomes. Ethnicity also affects fetal growth^24,25 and Japanese people tend to relatively small birth weights,²⁶ with greater likelihood of LBW under an absolute weight definition of this category. Therefore, we question the use of a single metric, LBW, for measuring perinatal performance and recommend the use of BW-for-GA z-scores, which can take several factors such as BW, sex, GA, and parity into account simultaneously. Moreover, we recommend the use of a direct measure of FGR because LBW is a consequence of FGR and/or preterm delivery, and these two etiologies should not be confused.⁹ In doing this, our study found an increase in the mean BW-for-GA z-scores indicating reduced risk of FGR even though LBW prevalence was high in our sample, indicating that the present perinatal situation in Japan is improving despite this elevated proportion of LBW infants.

We recommend a change in obstetric management and research practices to check for BW-for-GA z-scores and proportion of FGR in addition to the proportion of LBW.

In this study, FGR was defined as a poor prognosis factor. Japan still has a certain number of FGR infants, who have many short- and long-term complications.⁹ A decrease in FGR will contribute to the further improvement in perinatal outcomes. Therefore, further detailed information on FGR such as whether it is symmetrical or asymmetrical, complicates congenital diseases or not, and its presence in multiple pregnancy should be assessed in future research.

Although the present study is a whole national data without bias, data about the delivery method: normal delivery or CS was not included in the data, and discussion on CS includes speculation, which is a limitation for this study.

Assessing perinatal prognosis using a single metric, LBW, is no longer appropriate, and the presence of FGR and/or BW-for-GA should be taken into consideration.

BW: birth weight, CS: cesarean section, DOHaD: developmental origins of health and disease

FGR: fetal growth retardation, GA: gestational age, BW: low birth weight

MHLW: the Ministry of Health, Labour, and Welfare, PB: preterm birth

TOLAC: trial of labor after cesarean section

Ethics approval: Approved by the Ethic Committee of Tokyo Metropolitan Toshima Hospital (Approval number: Rin-jin 6-36).

Consent to participate, consent for publication: Not applicable (No individual details)

Availability of data and materials: The data that support the findings of this study are available from the MHLW. Restrictions apply to the availability of these data, which were used under license for this study. Data are available with the permission of the MHLW.

Competing interests: The authors declare that they have no competing interests.

Funding: JSPS KAKENHI Grant Number 24K11053

Authors' contributions

Conception and design: HS, SG, TS. Data curation and formal analysis: HS, YM, MS, KS, SG, DY. Funding acquisition: HS, DY. Investigation: YM, DY. Methodology: DY, SG. Project administration: HS, TS, DY. Resources: YM, HS, KS. Software: DY. Supervision: HS, DY, TS.

Validation: MS, KS, HS, TS. Visualization: YM, DY. Writing original draft: YM, HS, MS, DY.

Writing review and editing: KS, TS, SG.

All authors read and approved the final manuscript.

Authors' information

Hiromichi Shoji and Yayoi Murano are neonatologists. Toshiaki Shimizu is a pediatrician.

Miho Sassa is a midwife, and Ken Sakamaki is a gynecologist.

Daisuke Yoneoka and Stuart Gilmour are statisticians.

All the authors gathered the knowledge in this study.

Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

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No competing interests reported.

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Usefulness perinatal prognosis assessment using z-score over current low birth weight metric: a descriptive study

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