Physical development of preterm monochorionic diamniotic twins at birth: retrospective cohort study

INTRODUCTION

The physical development of newborn babies is fundamental in characterizing their state of health. Anthropometric data are commonly obtained in the first minutes of life following Apgar score calculation, which have high clinical and diagnostic significance. The parameters of physical development are thought to be predetermined by inherited genetic information and realized depending on performance under ambient conditions [1][2]. Intrauterine growth constitutes an essential stage affecting the variable growth process and the morphofunctional maturation of fetal organs and systems [3][4]. To date, much controversy surrounds the estimation of anthropometric parameters in multiple newborns, specifically in monochorionic placentation, due to specific complications arising in the antenatal period: twin-to-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) [5][6]. Intrauterine complications leading to changes in the anthropometric data of newborns largely determine their future health status and quality of life¹ [7][8]. In routine clinical practice, neonatologists can use the INTERGROWTH-21st project to assess the physical development of newborns. Since changes in the physical development parameters of preterm neonates are associated with a high risk of maladaptation, as well as neonatal incidence and mortality [9][10], a study was conducted in order to determine the potential of specific intrauterine complications in predicting the physical development of preterm monochorionic diamniotic twins [13][14].

Taking specific intrauterine complications into account, the study aims to estimate the physical development parameters of preterm monochorionic diamniotic twins according to standards proposed within the INTERGROWTH-21st project.

METHODS

Study design

A cross-sectional, retrospective cohort study was conducted.

Study conditions

The study was conducted at the Ural Research Institute of Maternal and Infant Care (Ministry of Health of the Russian Federation), analyzing the medical records of newborn monochorionic diamniotic twins delivered there in 2018–2021.

Eligibility criteria

Inclusion criteria

Preterm monochorionic diamniotic twins.

Exclusion criteria

Full-term monochorionic diamniotic twins, newborns in singleton pregnancies, newborn dichorionic twins, and twin reversed arterial perfusion sequence.

Removal criteria

Patients whose medical records lacked information necessary for the analysis.

Description of eligibility criteria (diagnostic criteria)

Birth anthropometric data documented in medical records were entered into the study database: body weight, body length, head circumference, as well as sex and gestational age of patients.

Selection of group members

The main cohort was retrospectively divided into three groups depending on the presence of specific intrauterine complications: twin-to-twin transfusion syndrome (TTTS), selective intrauterine growth restriction (sIUGR), and the absence of the specified complications associated with monochorionic multiple pregnancies. Group I comprises 56 pairs of monochorionic twins treated for TTTS using the laser coagulation of placental anastomoses at a gestational age of 16–21 weeks, whereas Group II consists of 38 monochorionic twin pairs with sIUGR in one of the fetuses: birth weight values are found within the extremely low (P < 3), or low (P < 10) centile band. Group III includes 56 pairs of monochorionic twins with no antenatal complications (TTTS and sIUGR).

Target parameters in the study

Main parameter in the study

The main birth parameters of physical development were estimated according to the INTERGROWTH-21st project: weight (kg), length (cm), head circumference (cm), and weight-length ratio (kg/m), indicating harmonious physical development.

Additional parameters in the study

Sex and gestational age depending on the presence or absence of specific complications: TTTS, sIUGR, and the absence of the specified complications.

Methods for measuring the parameters

Each patient was examined for body weight, body length, head circumference, and weight-length ratio under the INTERGROWTH-21st project; sex and gestational age of preterm monochorionic diamniotic twins, as well as the presence/absence of specific antenatal complications, were obtained from medical records.

Variables (predictors, confounders, and effect modifiers)

The birth parameters of physical development covered by the INTERGROWTH-21st project.

Statistical procedures

Principles behind sample size determination

The sample size was not determined in advance.

Statistical methods

The obtained data were statistically processed on a personal computer via variation statistics methods using Microsoft Excel spreadsheets (Microsoft, USA) and an online service available at https://medstatistic.ru. Qualitative parameters were described in terms of the absolute and relative frequencies of their values. The distribution of the examined anthropometric data differs from the normal distribution. The results are presented as a median of the interquartile range [ 25th percentile; 75th percentile], odds ratio (OR), and a 95% confidence interval (CI). The equality of medians was checked for several samples using the non-parametric Kruskal-Wallis test designed for independent populations. Differences were considered to be statistically significant at p < 0.05 and P < 0.01.

RESULTS

Sampling

According to the protocol, 148 pairs of preterm monochorionic twins (296 patients) were initially included in the study; however, the final analysis included the parameters of 292 newborns (Fig. 1).

Characteristics of the study sample

According to the obtained data, intrauterine fetal death was observed in two recipient fetuses, three donor fetuses, and one fetus exhibiting sIUGR signs. The overall mortality rate in the MDT group amounted to 2.03%, including 4.5% in Group I and 1.3% in Group II.

Main study results

The target parameters were estimated in relation to the following aspects: donor/recipient; newborns with/without sIUGR; twin having a greater/lower birth weight. In addition, Groups I, II, and III were compared in terms of body weight: a donor from Group I — a patient with sIUGR from Group II — a twin having a lower birth weight from Group III; a recipient from Group I — a twin without sIUGR from Group II — a newborn having a greater birth weight from Group III.

For all the examined groups, highly significant body weight differences were revealed in the subgroups of monochorionic twins (p < 0.001). In Group II, sIUGR was observed in both fetuses in three pairs (7.9%) at a gestational age of 33–34 weeks. All newborns with sIUGR had a birthweight of <10th centile, which was significantly (p < 0.001) lower than that of Group III twins having a lower body weight. In 21 donors (39.6%), body weight values were also found within a low centile band of P3- <10; no significant differences in this parameter were revealed from newborns with sIUGR.

The body weight of newborns indicates the development of the musculoskeletal system, subcutaneous tissue, and internal organs; the estimation of this parameter according to centile bands under the INTERGROWTH-21st project provides neonatologists with meaningful additional information about the antenatal period [15][16].

Birth weight values were found within the 10–90 centile band for the majority of recipients, Group III patients, and Group II newborns exhibiting no signs of sIUGR.

As well as birth weight, body length constitutes a fundamental criterion in the comprehensive health assessment of newborns.

Highly significant body length differences were revealed between the monochorionic twin subgroups in Groups I, II, and III (p < 0.001). All newborns with sIUGR exhibited symmetrical growth restrictions (body weight and length), as well as falling into the category of newborns light for gestational age (ICD-10 code — P05.0). These facts are consistent with the literature on the occurrence of fetal complications in newborns with sIUGR in early pregnancy, commonly during the first trimester [17][18]. In the donor group treated for TTTS, 26 (49.1%) neonates were also classified as newborns light for gestational age, which may result from the early onset of the transfusion syndrome. Only one recipient (1.9%) was found to be a newborn light for gestational age (ICD-10 code — P05.0), while other groups exhibited no such signs.

The harmonicity of physical development in newborns was estimated according to weight-height charts [19].

Harmonious development was observed in the majority of monochorionic twins from all groups, with the exception of newborns exhibiting the signs of sIUGR. Disharmonious and markedly disharmonious development was most common in newborns with sIUGR and, to a lesser extent, in donors (OR — 9.2; 95% CI — 3.2–24.3; p < 0.05); in monochorionic twins from other groups, it occurred in individual cases.

The analysis of head circumference also revealed significant differences between examined monochorionic twins.

Highly significant head circumference differences were revealed between the monochorionic twin subgroups in Groups I, II, and III (p < 0.001). In the group of neonates treated for TTTS, head circumference was found to be within the normal interval (p10–90) in 41 recipients (75.9%) and 38 donors (71.7%). In Group II, patients with sIUGR were significantly more likely to have a head circumference of P < 10 (OR –3.7; 95% CI — 1.4–9.7; p < 0.05): in 21 patients with sIUGR (56.8%) and 10 newborns (26.3%) without sIUGR. In Group III, all patients predominantly exhibited a range of normal head circumference values: in the monochorionic twins of greater weight — 50 (86.2%); in the monochorionic twins of lower weight — 53 (91.4%).

A physiological increase in head circumference during the antenatal period indicates active cell differentiation in the central nervous system, which is of fundamental importance for predicting cognitive development in infancy and early childhood [20][21]. In the event that intrauterine growth restriction is systemic in nature and does not correspond to the inherent genetic program for organism development, the long-term rehabilitation prognosis may be poor [20].

A symmetrical decrease in the values of birth centiles for head circumference, body weight, and body length was found in Groups I and II: in 13 (35.1%) newborns with sIUGR as compared to 1 MDT (2.6%) without sIUGR (OR — 20.0; 95% CI — 2.46–163.3; p < 0.05); in 12 donors (22.6%) as compared to 1 (1.9%) recipient (OR — 15.5; 95% CI — 1.94–124.2; p < 0.05). Group III revealed no newborns with similar changes. The delayed growth rate of head circumference may subsequently contribute to the development of neurological deficit, requiring prolonged dynamic monitoring^{2 3} [21][22].

Additional study parameters

The distribution of patients by gestational age is shown in Table 5.

The gestational age of monochorionic twins in uncomplicated pregnancies was significantly higher than that in the group of newborns treated for TTTS (p < 0.001) and with sIUGR (p = 0.01). Extremely preterm newborns (less than 28 weeks of gestation) were noted only in the group of monochorionic twins suffering from specific antenatal complications. No significant differences were observed between the groups in the number of very preterm neonates (28 weeks 0 days to 31 weeks 6 days). Births were moderately preterm for 42.9% of newborns treated for TTTS (OR — 4.6; 95% CI — 2.05–10.41; p < 0.05) and for 57.9% of neonates with sIUGR (OR — 2.52; 95% CI — 1.03–6.14; p  <  0.05) as compared to 77.6% of Group III neonates.

Boys accounted for 26 pairs (46.4%) in the group of newborns treated for TTTS, 23 pairs (60.5%) in the group with sIUGR, and 30 pairs (51.7%) in the group suffering from no antenatal complications; thus, no significant sex-specific differences were revealed.

DISCUSSION

Main findings of the study

The study was aimed at assessing physical development in preterm monochorionic diamniotic twins with and without TTTS and sIUGR under the INTERGROWTH-21st project. The INTERGROWTH-21st project provides a means to comprehensively analyze anthropometric data in preterm monochorionic twins, revealing characteristics associated with antenatal complications.

Research limitations

The study has several limitations. This single-center study conducted in 2018–2021 used a small number of patients, which may affect the final results, thus limiting the potential to extend these findings to a larger sample.

Discussion of the main study findings

The anthropometric data of newborns are used to assess the adequacy of fetal and neonatal growth, predict delayed growth abnormalities, as well as to assess neonatal incidence and mortality. The high rate of perinatal incidence and mortality in monochorionic multiple pregnancies is attributed both to a high frequency of preterm births and, to a large extent, specific complications in monochorionic placentation [11][12]. The obtained data indicate varying physical development disorders in preterm monochorionic twins associated with the complicated antenatal period. The use of international standards governing neonatal growth under INTERGROWTH-21st project enables a more effective assessment of the impact made by specific antenatal complications (TTTS and sIUGR) on the physical development of monochorionic diamniotic twins. The feeding and nursing of preterm monochorionic diamniotic twins classified as newborns light for gestational age, as well as newborns with disharmonious and markedly disharmonious physical development, should be different from that of gestational-age appropriate neonates [23]. In the group of monochorionic diamniotic twins, preterm neonates born following antenatal complications deserve increased attention: donors (TTTS) and patients exhibiting the signs of sIUGR. In order to prevent diseases commonly occurring in preterm newborns characterized by deficient physical development, the daily food ration should be maximally enriched with the permissible amounts of protein and energy per actual body weight.

As newborns’s harmonious development in later years can be largely determined by birth anthropometric parameters [20], it is imperative to prolong the physical development assessment under the INTERGROWTH-21st project in preterm monochorionic twins after antenatal complications, which will provide a means to optimize diagnosis and treatment for this group of patients.

CONCLUSION

Monochorionic diamniotic twin pairs include newborns having a higher and lower body weight. In the newborns of a lower birth weight, specific complications associated with monochorionic multiple pregnancy result in disharmonious development due to the lack of nourishment (22.6% in the TTTS group and 73.0% in the sIUGR group), as well as delayed head circumference growth in 56.8% of neonates with sIUGR.