Gestational weight gain standards based on women enrolled in the Fetal Growth Longitudinal Study of the INTERGROWTH-21^st Project: a prospective longitudinal cohort study

Abstract

Introduction

Associations between insufficient or excessive gestational weight gain (GWG) and short and long term maternal and child health outcomes are well described.¹ Insufficient weight gain has been linked with increased risks of low birth weight, small for gestational age, and preterm birth, while excessive gain has been associated with large for gestational age, gestational diabetes, preterm birth, caesarean section, infant mortality, postpartum weight retention, and childhood obesity.^{2 3 4 5 6 7 8 9} Pregnant women are therefore routinely weighed in clinical settings. The benefits of doing so, however, are debatable in the absence of appropriate guidelines or even agreement on what constitutes adequate weight gain.^{10 11}

In 1970, the Institute of Medicine/National Research Council reviewed the available evidence on GWG that resulted in good pregnancy outcomes, with subsequent revisions in 1990 and 2009.^{1 12 13} The latest guidelines evaluated the trade offs between maternal and child health outcomes and weight gain during pregnancy, including the risks of small for gestational age and preterm birth with inadequate GWG and the increased rates of caesarean section and postpartum weight retention with excessive GWG. Based on a recent systematic review, however, these guidelines were all derived from country specific studies that varied in sample selection, study design, and methods of data collection and statistical analysis.¹⁴ In the United Kingdom, “routine weighing during pregnancy should be confined to circumstances in which clinical management is likely to be influenced.”¹⁵ In countries where routine weighing is recommended, most current guidelines are based on relating observed GWG to pregnancy outcomes and then determining the range of weight gain with the lowest perinatal risk,^{1 16 17 18} although other authors have attempted to select populations with good perinatal outcomes and then retrospectively determine the associated GWG range.^{19 20 21 22}

The World Health Organization recommends that a reference for GWG be based on prospective longitudinal studies of selected populations with a low incidence of maternal and fetal complications, where anthropometric measures are collected before and during pregnancy and postpartum.²³ The same “prescriptive” approach was adopted by WHO in producing international growth standards for children aged 0-5 years that have now been adopted by more than 125 countries worldwide,²⁴ and by the International Fetal and Newborn Growth (INTERGROWTH-21^st) Consortium for the 21^st Century in producing standards for early pregnancy dating,²⁵ fetal growth,²⁶ newborn size,²⁷ and postnatal growth for preterm infants.²⁸ We examined data on GWG obtained, according to WHO recommendations, from healthy pregnant women who were free from identifiable major medical, nutritional, or social and major environmental risk factors.^{26 29 30} The women had pregnancies with good maternal and perinatal outcomes.³¹ Based on these data, we report GWG patterns from normal weight women.

Methods

Results

A total of 13 108 pregnant women at <14 weeks’ gestation were screened (fig 1​1),), and 4607 met the eligibility criteria, provided consent, and were enrolled in the Fetal Growth Longitudinal Study. The contribution from each site to the total enrolled sample population ranged from 311 (7%) for the US to 640 (14%) for the UK.

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Fig 1 Flowchart for selecting women included in study of gestational weight gain

The most common reasons for ineligibility were maternal height <153 cm (1022/8501; 12%), BMI ≥30 (1009/8501; 12%), and age <18 or >35 years (915/8501; 11%) at screening. During the pregnancy, 71 women were lost to follow-up or withdrew consent and 36 were excluded (during pregnancy 29 had severe medical conditions, six took up smoking, and one used recreational drugs). After exclusion of 78 miscarriages, terminations, or stillbirths, there were 4422 live singleton births of which a further 101 were excluded because of congenital malformations. Of the 4321 remaining women, eight were excluded from the analysis (four with only one weight measurement during pregnancy and four who were obvious outliers because of illogical values that could not be corrected during data cleaning). We excluded nine observations with extreme weight changes (defined as a gain or loss of >5 kg/week).

Our final sample therefore consisted of 4313 women who contributed 24 977 weight measurements. Of these, 3097 (72%) women had normal weight in the first trimester. Here we report the analyses pertaining to these normal weight women whose data were used to construct the international GWG standard.

The demographic characteristics of the study cohort were similar across the eight sites and have been reported elsewhere.³¹ Women had a median of six weight measurements (range 2-7); median gestational age at first antenatal visit was 11.9 weeks (SD 1.4 weeks); mean maternal age was 28.2 (SD 3.8) years; 97% (3020/3097) were married or living with a partner, and 72% (2230/3097) were nulliparous. Table 1​1 shows sociodemographic information and pregnancy and perinatal events. Fig 2​2 shows an example of the crude weight gain trajectories of a simple random sample of 100 normal weight women, illustrating the longitudinal design of the study.

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Fig 2 Trajectories of gestational weight gain of 100 randomly selected normal weight healthy women with uncomplicated live singleton births

We explored the variation in GWG among the sites; the variance within sites (59.6%) was six times higher than the variance between sites (9.6%). The all sites’ SD for GWG ranged from 1.45 kg at 14-19⁺⁶ weeks’ gestation to 1.61 kg at 34-40 weeks’ gestation. Within five gestational age windows from 14 weeks to 40⁺⁰ weeks, representing 40 comparisons, 37 had standardised site differences (SSDs) ≤0.5 (as prespecified in the protocol) of the SD of all sites combined (fig 3​3,, table 2​2).). The three comparisons that were higher than 0.5 SSD were from China, but the difference was <0.5 at 14-18⁺⁶ weeks’ gestation and at 34-40 weeks’ gestation (0.34 and 0.21, respectively).

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Fig 3 Standardised site difference (SSD) for gestational weight gain in the Fetal Growth Longitudinal Study of the INTERGROWTH-21^st Project. SSD calculated by (site mean of gestational weight gain at each gestational age interval minus all sites mean of gestational weight gain at the same gestational age interval)/all sites’ SD of gestational weight gain at the same gestational age interval. SSD was adjusted at median gestational age for all sites at each gestational age interval

The mean GWGs were 1.64 kg, 2.86 kg, 2.86 kg, 2.59 kg, and 2.56 kg for the gestational age windows 14-18⁺⁶ weeks, 19-23⁺⁶ weeks, 24-28⁺⁶ weeks, 29-33⁺⁶ weeks, and 34-40⁺⁰ weeks, respectively (table 2​2).). Of all the weight measurements, 71.7% (10 639/14 846) and 94.9% (14 085/14 846) fell within the expected 1 SD and 2 SD thresholds, respectively, which compares well with 68% and 95% theoretically expected under normality assumptions. On average, across all gestational ages, the absolute magnitude of differences between the observed (empirical) and smoothed centiles was 0.18 kg for the median, 0.37 kg for the 3rd centile, and 0.06 kg for the 97th centile (fig 4​4).

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Fig 4 Fitted 3rd (bottom dashed line), 50th (middle dashed line), and 97th (top dashed line) smoothed centile curves for gestational weight gain among normal weight women. Large blue circles show empirical values for each week of gestation, and small grey circles show actual observations

Table 3​3 provides the values of the smoothed week specific GWG according to gestational age of selected centiles (that is, 3rd, 10th, 25th, 50th, 75th, 90th, and 97th), which are shown graphically in figure 5​5.. We have also provided the corresponding equations for the mean and SD from the multilevel regression model (table 4​4),), allowing for calculation of any desired centiles according to gestational age in exact weeks. For example, centiles can be calculated as mean ±z×SD, where z is −1.88, −1.645, −1.28, 0, 1.28, 1.645, and 1.88 for the 3rd, 5th, 10th, 50th, 90th, 95th, and 97th centiles, respectively.

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Fig 5 Smoothed centile curves at 3rd, 10th, 50th, 90th, and 97th centiles for gestational weight gain among healthy normal weight women with uncomplicated live singleton births

The sensitivity analyses performed to assess the impact of potential misclassification of BMI status resulted in 30% (932/3097) of women being excluded from the normal weight group and 53% (n=639/1216) of women being added from the overweight group to form a reclassified group of normal weight women (n=2804 women, 17 579 observations). The resultant centile values were remarkably similar and indistinguishable when we superimposed them on the normal weight GWG chart. Sensitivity results when we excluded women with caesarean sections had minimal effect compared with results using all the data (data not shown).

Tables containing the mean and SD, centile values, and z scores by gestational age, expressed in completed weeks’ gestation (as recommended by WHO ICD10⁴⁴), and printable charts are available at www.intergrowth21.org.

Discussion

Notes

We thank the health authorities in Pelotas, Brazil; Beijing, China; Nagpur, India; Turin, Italy; Nairobi, Kenya; Muscat, Oman; Oxford, UK; and Seattle, US, who facilitated the project by allowing participation of these study sites as collaborating centres. We are extremely grateful to Philips Medical Systems who provided the ultrasound equipment and technical assistance throughout the project. We also thank MedSciNet UK for setting up the INTERGROWTH-21^st website and for the development, maintenance, and support of the online data management system. We thank the parents and infants who participated in the studies and the more than 200 members of the research teams who made the implementation of this project possible. The participating hospitals included: Brazil, Pelotas (Hospital Miguel Piltcher, Hospital São Francisco de Paula, Santa Casa de Misericórdia de Pelotas, and Hospital Escola da Universidade Federal de Pelotas); China, Beijing (Beijing Obstetrics and Gynaecology Hospital, Shunyi Maternal and Child Health Centre, and Shunyi General Hospital); India, Nagpur (Ketkar Hospital, Avanti Institute of Cardiology Private Limited, Avantika Hospital, Gurukrupa Maternity Hospital, Mulik Hospital and Research Centre, Nandlok Hospital, Om Women’s Hospital, Renuka Hospital and Maternity Home, Saboo Hospital, Brajmonhan Taori Memorial Hospital, and Somani Nursing Home); Kenya, Nairobi (Aga Khan University Hospital, MP Shah Hospital and Avenue Hospital); Italy, Turin (Ospedale Infantile Regina Margherita Sant’ Anna and Azienda Ospedaliera Ordine Mauriziano); Oman, Muscat (Khoula Hospital, Royal Hospital, Wattayah Obstetrics and Gynaecology Poly Clinic, Wattayah Health Centre, Ruwi Health Centre, Al-Ghoubra Health Centre and Al-Khuwair Health Centre); UK, Oxford (John Radcliffe Hospital); and US, Seattle (University of Washington Hospital, Swedish Hospital, and Providence Everett Hospital).

Full acknowledgment of all those who contributed to the development of the INTERGROWTH-21^st Project protocol appears at www.intergrowth21.org.uk

Members of the International Fetal and Newborn Growth Consortium for the 21^st Century (INTERGROWTH-21^st) and its committees

Scientific advisory committee M Katz (chair from January 2011), MK Bhan, C Garza, S Zaidi, A Langer, PM Rothwell (from February 2011), D Weatherall (chair until December 2010).

Steering committee ZA Bhutta (chair), J Villar (principal investigator), S Kennedy (project director), DG Altman, FC Barros, E Bertino, F Burton, M Carvalho, L Cheikh Ismail, WC Chumlea, MG Gravett, YA Jaffer, A Lambert, P Lumbiganon, JA Noble, RY Pang, AT Papageorghiou, M Purwar, J Rivera, CG Victora.

Executive committee J Villar (chair), DG Altman, ZA Bhutta, L Cheikh Ismail, S Kennedy, A Lambert, JA Noble, AT Papageorghiou.

Project coordinating unit J Villar (head), S Kennedy, L Cheikh Ismail, A Lambert, AT Papageorghiou, M Shorten, L Hoch (until May 2011), HE Knight (until August 2011), EO Ohuma (from September 2010), C Cosgrove (from July 2011), I Blakey (from March 2011), D Bishop (from February 2014).

Data analysis group DG Altman (head), EO Ohuma, J Villar.

Data management group DG Altman (head), F Roseman, N Kunnawar, SH Gu, JH Wang, MH Wu, M Domingues, P Gilli, L Juodvirsiene, L Hoch (until May 2011), N Musee (until June 2011), H Al-Jabri (until October 2010), S Waller (until June 2011), C Cosgrove (from July 2011), D Muninzwa (from October 2011), EO Ohuma (from September 2010), D Yellappan (from November 2010), A Carter (from July 2011), S Ash (from August 2011), D Reade (from June 2012), R Miller (from June 2012).

Ultrasound group AT Papageorghiou (head), L Salomon (senior external advisor), A Leston, A Mitidieri, F Al-Aamri, W Paulsene, J Sande, WKS Al-Zadjali, C Batiuk, S Bornemeier, M Carvalho, M Dighe, P Gaglioti, N Jacinta, S Jaiswal, JA Noble, K Oas, M Oberto, E Olearo, MG Owende, J Shah, S Sohoni, T Todros, M Venkataraman, S Vinayak, L Wang, D Wilson, QQ Wu, S Zaidi, Y Zhang, P Chamberlain (until September 2012), D Danelon (until July 2010), I Sarris (until June 2010), J Dhami (until July 2011), C Ioannou (until February 2012), CL Knight (from October 2010), R Napolitano (from July 2011), S Wanyonyi (from May 2012), C Pace (from January 2011), V Mkrtychyan (from June 2012).

Anthropometry group L Cheikh Ismail (head), WC Chumlea (senior external advisor), F Al-Habsi, ZA Bhutta, A Carter, M Alija, JM Jimenez-Bustos, J Kizidio, F Puglia, N Kunnawar, H Liu, S Lloyd, D Mota, R Ochieng, C Rossi, M Sanchez Luna, YJ Shen, HE Knight (until August 2011), DA Rocco (from June 2012), IO Frederick (from June 2012).

Neonatal group ZA Bhutta (head), E Albernaz, M Batra, BA Bhat, E Bertino, P Di Nicola, F Giuliani, I Rovelli, K McCormick, R Ochieng, RY Pang, V Paul, V Rajan, A Wilkinson, A Varalda (from September 2012).

Environmental Health Group B Eskenazi (head), LA Corra, H Dolk, J Golding, A Matijasevich, T de Wet, JJ Zhang, A Bradman, D Finkton, O Burnham, F Farhi.

Participating countries and local investigators

Brazil: FC Barros (principal investigator), M Domingues, S Fonseca, A Leston, A Mitidieri, D Mota, IK Sclowitz, MF da Silveira.

China: RY Pang (principal investigator), YP He, Y Pan, YJ Shen, MH Wu, QQ Wu, JH Wang, Y Yuan, Y Zhang.

India: M Purwar (principal investigator), A Choudhary, S Choudhary, S Deshmukh, D Dongaonkar, M Ketkar, V Khedikar, N Kunnawar, C Mahorkar, I Mulik, K Saboo, C Shembekar, A Singh, V Taori, K Tayade, A Somani.

Italy: E Bertino (principal investigator), P Di Nicola, M Frigerio, G Gilli, P Gilli, M Giolito, F Giuliani, M Oberto, L Occhi, C Rossi, I Rovelli, F Signorile, T Todros.

Kenya: W Stones and M Carvalho (co- principal investigators), J Kizidio, R Ochieng, J Shah,, S Vinayak, N Musee (until June 2011), C Kisiang’ani (until July 2011), D Muninzwa (from August 2011).

Oman: YA Jaffer (principal investigator), J Al-Abri, J Al-Abduwani, FM Al-Habsi, H Al-Lawatiya, B Al-Rashidiya, WKS Al-Zadjali, FR Juangco, M Venkataraman, H Al-Jabri (until October 2010), D Yellappan (from November 2010).

UK: S Kennedy (principal investigator), L Cheikh Ismail, AT Papageorghiou, F Roseman, A Lambert, EO Ohuma, S Lloyd, R Napolitano (from July 2011), C Ioannou (until February 2012), I Sarris (until June 2010).

US: MG Gravett (principal investigator), C Batiuk, M Batra, S Bornemeier, M Dighe, K Oas, W Paulsene, D Wilson, IO Frederick, HF Andersen, SE Abbott, AA Carter, H Algren, DA Rocco, TK Sorensen, D Enquobahrie, S Waller (until June 2011).

Contributors: JV and SHK were responsible for conceiving the INTERGROWTH-21^st Project. JV, SHK, DGA, and JAN prepared the original protocol with later input from ATP, LCI, FCB, and ZAB. JV, ATP, LCI, AL, and ZAB supervised and coordinated the project’s overall undertaking. EOO performed the statistical analysis in collaboration with DGA. EOO, and DGA were responsible for data management and analysis in collaboration with JV. RP, FCB, WS, YAJ, MGG, and MP were collaborators and implemented the project in their respective countries. LCI, DCB, and EOO wrote the paper in collaboration with BFA and KR, with input from all co-authors. All co-authors read the report and made suggestions about its content. JV is guarantor.

Funding: This project was supported by the Bill and Melinda Gates Foundation to the University of Oxford. The sponsor played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval: The INTERGROWTH-21^st Project was approved by the Oxfordshire research ethics committee ‘C’ (reference: 08/H0606/139), the research ethics committees of the individual participating institutions, and the corresponding regional health authorities where the project was implemented. All participants gave informed consent before taking part.

Transparency: The manuscript’s guarantor affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Data sharing: The relevant anonymised patient level data are available on reasonable request from the corresponding author.

References